Conference Coverage

SAN DIEGO — During her dermatology residency training, Caroline Piggott, MD, was taught that the classic signs of a Spitz nevus were a symmetric arrangement of colors and structures, followed by certain features on dermoscopy.

“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”

However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.

When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”

If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”

However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).

“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”

Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm² in size.

In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”

If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”

Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO — During her dermatology residency training, Caroline Piggott, MD, was taught that the classic signs of a Spitz nevus were a symmetric arrangement of colors and structures, followed by certain features on dermoscopy.

“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”

However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.

When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”

If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”

However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).

“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”

Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm² in size.

In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”

If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”

Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO — During her dermatology residency training, Caroline Piggott, MD, was taught that the classic signs of a Spitz nevus were a symmetric arrangement of colors and structures, followed by certain features on dermoscopy.

“For a pigmented Spitz nevus, we were taught to look for a starburst pattern, a central area of homogeneous pigment, and peripheral symmetrical streaks or pseudopods,” Dr. Piggott, an adult and pediatric dermatologist at Scripps Clinic, San Diego, said at the annual Cutaneous Malignancy Update. “For Spitz nevi without pigment, we were taught to look for symmetric dotted vessels.”

However, results from a retrospective study published in 2015 gave her pause in relying on dermoscopy alone for assessing Spitz nevi. Researchers from Italy, Japan, and Brazil studied excision specimens of 384 Spitzoid-looking lesions in patients 12 years and older. On histology, 86.7% were diagnosed as benign Spitz nevi and 13.3% were diagnosed as melanoma.

When the researchers looked at the dermoscopic images, many cases of atypical Spitz nevi were indistinguishable from the benign Spitz nevi. Now, Dr. Piggott said, “I respect the dermoscopy criteria, but I don’t rely solely on it.”

If a child presents with Spitzoid-looking lesion, biopsy is generally preferred to observation. “The traditional belief was that punch biopsy was preferable, followed by shave biopsy,” she said. “This is always on a case-by-case basis.”

However, results from a retrospective study of the records of 123 cases of biopsy-proven Spitz nevi with incomplete removal on biopsy suggests that the method of biopsy matters. The researchers found that the presence of residual lesion in the re-excision specimen was significantly higher when the initial biopsy was done by punch biopsy (90.9%) when compared with shave biopsy (48.9%) and formal excision (62.5%; P < .05).

“This suggests that shave may better than punch for the initial biopsy, but the study was limited by its retrospective design,” Dr. Piggott said at the meeting, which was hosted by Scripps Cancer Center. “Even today it remains controversial whether you should do a shave or punch biopsy.”

Parameters for diagnosing Spitzoid tumors that pathologists look for under the microscope are asymmetry, Clark’s level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, and mitoses that are atypical, deep, or that exceed 6 mm² in size.

In terms of treatment recommendations for children with biopsy-proven Spitz nevi, Dr. Piggott said that there is no consensus among pediatric dermatologists. If the biopsy comes back as a benign Spitz nevus, the most reasonable approach is observation, “especially if there is no clinical residue — no pigment on exam, no papule left over in the scar,” she said. “You also want to educate the family about the rare potential for transformation down the line. Monitor for recurrence and consider re-excision if recurrence occurs.”

If the initial Spitz nevus biopsy reveals any degree of atypia, excision is preferred. “In young children, you have to weigh the risks of anesthesia for removal,” she said. “If you’re unable to excise the lesion, close observation is recommended at 6 months or 1 year.”

Treatment for borderline atypical Spitz tumor is excision, she continued, but no outcomes data exist that document a survival benefit with sentinel lymph node (SLN) biopsy. “The decision on whether to do a SLN biopsy is usually made on a case-by-case basis,” Dr. Piggott said. “Nodal metastases from atypical Spitzoid tumors are not uncommon, but death from widespread disease is rare. If the SLN biopsy is positive, complete lymphadenectomy is associated with increased risk of morbidity and no evidence of increased survival. If lymph node disease is found, we in pediatric dermatology would consider referral to a pediatric oncologist for consideration of systemic therapy such as interferon or a newer immunotherapy.”

Dr. Piggott reported having no relevant disclosures.

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

SAN DIEGO — According to data from the American Cancer Society (ACS), cutaneous melanoma was the fifth most common cancer in 2023, with an estimated 97,610 new cases and 7,990 deaths, following cancer of the colorectal area, lung and bronchus, prostate, and breast.

“The incidence of melanoma seems to have continued to go up since the early 1990s,” David E. Kent, MD, a dermatologist at Skin Care Physicians of Georgia, Macon, said at the annual Cutaneous Malignancy Update. “The death rates have been flat and may have slightly decreased.”

In 2024, the ACS estimates that about 100,640 new melanomas will be diagnosed in the United States (59,170 in men and 41,470 in women), and about 8,290 people are expected to die of melanoma (5,430 men and 2,860 women). Meanwhile, the lifetime risk of melanoma is about 3% (1 in 33) for Whites, 0.1% (1 in 1,000) for Blacks, and 0.5% (1 in 200) for Hispanics. In 2019, there were an estimated 1.4 million people in the United States living with cutaneous melanoma, and the overall 5-year survival is 93.7%.

Epidemiologic studies show an increase in melanoma incidence, primarily among White populations. “This is believed to be due to sun exposure, changes in recreational behaviors, and tanning bed exposures,” said Dr. Kent, who holds a faculty position in the department of dermatology at the Medical College of Georgia, Augusta. Increased surveillance and diagnosis also play a role. In the medical literature, annual increases in melanoma incidence vary from 3%-7% per year, “which means that the rate is doubling every 10-20 years,” he said, noting that annual melanoma costs are approximately $3.3 billion.

While incidence rates are lower in non-White, non-Hispanic populations, poor outcomes are disproportionately higher in persons of color, according to a 2023 paper. Black individuals present at diagnosis with more advanced stage disease and are 1.5 times more likely to die from melanoma, he said, while Hispanics are 2.4 times more likely to present with stage III disease and 3.6 times more likely to have distant metastases. Persons of color also have higher rates of mucosal, acral lentiginous, and subungual melanoma.

Risk Factors

Known genetic risk factors for melanoma include having skin types I and II, particularly those with light hair, light eyes, and freckling, and those with a family history have a twofold increased risk. Also, up to 40% of genetic cases are from inherited mutations in CDKN2A, CDK4, BAP1 and MCR1. Other genetic-related risk factors include the number and size of nevi, having atypical nevus syndrome, DNA repair defects, large congenital nevi, and a personal history of melanoma.

Dr. Kent said that genetic testing for melanoma is warranted for individuals who meet criteria for the “rule of 3s.” He defined this as three primary melanomas in an individual, or three cases of melanoma in first- or second-degree relatives, or two cases of melanoma and one pancreatic cancer or astrocytoma in first or second-degree relatives, or one case of melanoma and two of pancreatic cancer/astrocytoma in first- or second-degree relatives.

The main environmental risk factor for melanoma is exposure to ultraviolet radiation. Individuals can track their UV exposure with a variety of wearable devices and apps, including SunSense One Digital UV Tracker, the SunSense App, the UV Index Widget, the SunSmart Global UV App, the SunKnown UV light photometer, and the EPA’s UV Index Mobile App. Other environment-related risk factors include having a high socioeconomic status (SES), being immunosuppressed, as well as exposure to heavy metals, insecticides, or hormones; and ones distance from the equator.

In a study published in 2023, researchers investigated the risk factors associated with first and second primary melanomas in 38,845 patients who were followed in Australia between 2011 and 2018. During a median follow-up of 7.4 years, 1212 patients (3.1%) had a single primary melanoma diagnosis and 245 (0.6%) had a secondary primary melanoma diagnosis. The researchers found that second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (defined as 1 mm or less) than first melanomas. In addition, having many self-reported moles at age 21 years was more strongly associated with second melanomas compared with first melanomas (hazard ratio, 6.36 vs 3.46, respectively; P = .01), as was having a high genetic predisposition (HR, 3.28 vs. 2.06; P = .03). Second melanomas were also more strongly associated with a history of multiple skin cancer excisions (HR, 2.63 vs 1.86; P = .05).

Dr. Kent noted that while sunscreen use protects against melanoma, a National Ambulatory Medical Care Survey in 2014 found that internists and pediatricians mentioned sunscreen at fewer than 0.1% of visits — even those with patients who have a diagnosis of skin disease. “Physicians need to do better,” he said at the meeting, which was hosted by the Scripps Cancer Center. “We as dermatologists have work to do to help educate them.”

Dr. Kent reported having no relevant disclosures.

ORLANDO, FLORIDA — For some people, acne carries a one-two punch. First, they experience acne that is significant enough to decrease their quality of life, followed by scarring that can last a lifetime. For those patients, dermatologists have several options: Subcision to lift the depression of the scar, laser treatment to lower the height of scar tissue, and injections to fill scars.

“In my practice, I find that these [acne scars] are probably the hardest things to treat. But along the way, I created a protocol that I would love to share with you today,” Robyn Siperstein, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Siperstein starts by identifying the type of acne scar — rolling scars, boxcar scars, or ice pick scars. Rolling scars tend to be shallower with no sharp edges; boxcar scars are deeper, more defined round or oval depressions; and ice pick scars, as the name suggests, look like someone stuck tiny ice picks into the skin, leaving a sunken or pitted appearance.

“It’s really important to categorize so that we know which ones are going to be effectively treated with different modalities and which ones aren’t, so that we can give our patients realistic expectations,” said Dr. Siperstein, a cosmetic dermatologist in private practice in Boca Raton, Florida, and a clinical affiliate associate professor of dermatology at Florida Atlantic University, Boca Raton.

“There’s not going to be one treatment that’s right for everything,” she said. Different approaches may be required even for the same patient because some people present with all three types of acne scars, she added.

Combining Treatments

When it comes to injecting dermal fillers into acne scars to lift the depressed areas, the US Food and Drug Administration approved a filler with polymethyl methacrylate filler and bovine collagen (Bellafill) for this indication (moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over age 21) in 2015. “And off-label, I use hyaluronic acid in my practice,” Dr. Siperstein said. Each filler “probably works a little bit better or differently on different types of scars.”

For rolling scars, she recommends hyaluronic acid (HA) dermal filler for everyone. “Of course, this is my opinion.” She was also a lead investigator in a randomized, placebo-controlled split-face study comparing HA filler with saline for correcting atrophic facial scars in 15 patients. The HA filler emerged superior, although there were some improvements with saline.

In her clinical experience, patients are happy with the results and ask, “Why didn’t the last four doctors do this?”

Boxcar scars are more challenging to fill with HA. In some cases, Dr. Siperstein is able to raise the depressed portion of the scar, but some of the vertical edges remain. In this scenario, she might combine treatments. Laser resurfacing, for example, might help convert boxcar scars into rolling scars, which then can be filled more successfully.

“Ice pick scars are tough,” Dr. Siperstein said. A punch removal technique can work in some cases, or she might try the “cross technique.” This involves placing acetic acid inside the scar using a Q-tip. “You have to be really careful,” she added, “because if you get it around the edges, it’s actually going to make the scar bigger.”
 

Choosing the Right Candidates

Selecting the right candidate for HA treatment of acne scars is essential. Dr. Siperstein shared the example of a lifeguard who had prominent acne scarring down the center of his chest. “He was embarrassed to go to the beach and take off his shirt. He said he felt like he had bullet holes in his chest.”

One month following treatment, “he had a really nice improvement, and now he feels really comfortable,” she said.

Some dermatologists might be reluctant to consider HA fillers for acne scarring because there is a misconception that HA is short-acting, lasting 6 months to 1 year before the effect wears off. That impression can persist from company-sponsored studies that limit follow-up to 6 months or 1 year “to get their drug to market,” she noted.

Also adding to this impression is that HA fillers in wrinkles may not last as long. Dr. Siperstein explained that wrinkles on the face are dynamic and constantly moving. In contrast, acne scars experience less movement, which helps the HA last longer. There is MRI evidence that shows HA fillers last over 2 years in the face, she added.

One tip to predict how well an acne scar might respond to filler injections is to squeeze it and look for the “dimple sign.” If the floor of the scar lifts up when squeezed, “we know that they’ll be a good candidate for hyaluronic acid filler.” Another tip is to inject HA in a retrograde technique high up in the skin. Inject tiny amounts — microdroplets — of the HA filler high on the dermis, she advised.

Deeper injections run the risk of raising the entire scar instead of filling it, she added.

Like many dermatologic procedures, before and after photos are essential to demonstrate improvements, Dr. Siperstein pointed out. Patients are often skeptical. “This happens a lot with acne scar patients. They’ve been to a million places that have promised results, they have not gotten them, and they are frustrated.”

Acne scars can result from picking, inflammation, or treatment. “This is what we see all day in clinic,” Dr. Siperstein said. “Somebody who had to undergo Accutane treatment but unfortunately is left with holes. This is a huge psychological burden on our patients,” she said, describing a younger patient who had scarring, which “led to depression — it was ruining his life.”

“His mom was willing to do whatever it took. And I said, You know what, I think filler will be enough,” Dr. Siperstein said. She counseled them that treatment would not make the scars disappear completely. But patients used to 10% improvements are very happy when their acne scars look 80% or 90% better, she added.

Dr. Siperstein received grant or research support and is a member of the speakers bureau for Allergan and Galderma. She is also a consultant/advisory board member for Allergan.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — For some people, acne carries a one-two punch. First, they experience acne that is significant enough to decrease their quality of life, followed by scarring that can last a lifetime. For those patients, dermatologists have several options: Subcision to lift the depression of the scar, laser treatment to lower the height of scar tissue, and injections to fill scars.

“In my practice, I find that these [acne scars] are probably the hardest things to treat. But along the way, I created a protocol that I would love to share with you today,” Robyn Siperstein, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Siperstein starts by identifying the type of acne scar — rolling scars, boxcar scars, or ice pick scars. Rolling scars tend to be shallower with no sharp edges; boxcar scars are deeper, more defined round or oval depressions; and ice pick scars, as the name suggests, look like someone stuck tiny ice picks into the skin, leaving a sunken or pitted appearance.

“It’s really important to categorize so that we know which ones are going to be effectively treated with different modalities and which ones aren’t, so that we can give our patients realistic expectations,” said Dr. Siperstein, a cosmetic dermatologist in private practice in Boca Raton, Florida, and a clinical affiliate associate professor of dermatology at Florida Atlantic University, Boca Raton.

“There’s not going to be one treatment that’s right for everything,” she said. Different approaches may be required even for the same patient because some people present with all three types of acne scars, she added.

Combining Treatments

When it comes to injecting dermal fillers into acne scars to lift the depressed areas, the US Food and Drug Administration approved a filler with polymethyl methacrylate filler and bovine collagen (Bellafill) for this indication (moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over age 21) in 2015. “And off-label, I use hyaluronic acid in my practice,” Dr. Siperstein said. Each filler “probably works a little bit better or differently on different types of scars.”

For rolling scars, she recommends hyaluronic acid (HA) dermal filler for everyone. “Of course, this is my opinion.” She was also a lead investigator in a randomized, placebo-controlled split-face study comparing HA filler with saline for correcting atrophic facial scars in 15 patients. The HA filler emerged superior, although there were some improvements with saline.

In her clinical experience, patients are happy with the results and ask, “Why didn’t the last four doctors do this?”

Boxcar scars are more challenging to fill with HA. In some cases, Dr. Siperstein is able to raise the depressed portion of the scar, but some of the vertical edges remain. In this scenario, she might combine treatments. Laser resurfacing, for example, might help convert boxcar scars into rolling scars, which then can be filled more successfully.

“Ice pick scars are tough,” Dr. Siperstein said. A punch removal technique can work in some cases, or she might try the “cross technique.” This involves placing acetic acid inside the scar using a Q-tip. “You have to be really careful,” she added, “because if you get it around the edges, it’s actually going to make the scar bigger.”
 

Choosing the Right Candidates

Selecting the right candidate for HA treatment of acne scars is essential. Dr. Siperstein shared the example of a lifeguard who had prominent acne scarring down the center of his chest. “He was embarrassed to go to the beach and take off his shirt. He said he felt like he had bullet holes in his chest.”

One month following treatment, “he had a really nice improvement, and now he feels really comfortable,” she said.

Some dermatologists might be reluctant to consider HA fillers for acne scarring because there is a misconception that HA is short-acting, lasting 6 months to 1 year before the effect wears off. That impression can persist from company-sponsored studies that limit follow-up to 6 months or 1 year “to get their drug to market,” she noted.

Also adding to this impression is that HA fillers in wrinkles may not last as long. Dr. Siperstein explained that wrinkles on the face are dynamic and constantly moving. In contrast, acne scars experience less movement, which helps the HA last longer. There is MRI evidence that shows HA fillers last over 2 years in the face, she added.

One tip to predict how well an acne scar might respond to filler injections is to squeeze it and look for the “dimple sign.” If the floor of the scar lifts up when squeezed, “we know that they’ll be a good candidate for hyaluronic acid filler.” Another tip is to inject HA in a retrograde technique high up in the skin. Inject tiny amounts — microdroplets — of the HA filler high on the dermis, she advised.

Deeper injections run the risk of raising the entire scar instead of filling it, she added.

Like many dermatologic procedures, before and after photos are essential to demonstrate improvements, Dr. Siperstein pointed out. Patients are often skeptical. “This happens a lot with acne scar patients. They’ve been to a million places that have promised results, they have not gotten them, and they are frustrated.”

Acne scars can result from picking, inflammation, or treatment. “This is what we see all day in clinic,” Dr. Siperstein said. “Somebody who had to undergo Accutane treatment but unfortunately is left with holes. This is a huge psychological burden on our patients,” she said, describing a younger patient who had scarring, which “led to depression — it was ruining his life.”

“His mom was willing to do whatever it took. And I said, You know what, I think filler will be enough,” Dr. Siperstein said. She counseled them that treatment would not make the scars disappear completely. But patients used to 10% improvements are very happy when their acne scars look 80% or 90% better, she added.

Dr. Siperstein received grant or research support and is a member of the speakers bureau for Allergan and Galderma. She is also a consultant/advisory board member for Allergan.
 

A version of this article appeared on Medscape.com.

ORLANDO, FLORIDA — For some people, acne carries a one-two punch. First, they experience acne that is significant enough to decrease their quality of life, followed by scarring that can last a lifetime. For those patients, dermatologists have several options: Subcision to lift the depression of the scar, laser treatment to lower the height of scar tissue, and injections to fill scars.

“In my practice, I find that these [acne scars] are probably the hardest things to treat. But along the way, I created a protocol that I would love to share with you today,” Robyn Siperstein, MD, said at the annual ODAC Dermatology, Aesthetic & Surgical Conference.

Dr. Siperstein starts by identifying the type of acne scar — rolling scars, boxcar scars, or ice pick scars. Rolling scars tend to be shallower with no sharp edges; boxcar scars are deeper, more defined round or oval depressions; and ice pick scars, as the name suggests, look like someone stuck tiny ice picks into the skin, leaving a sunken or pitted appearance.

“It’s really important to categorize so that we know which ones are going to be effectively treated with different modalities and which ones aren’t, so that we can give our patients realistic expectations,” said Dr. Siperstein, a cosmetic dermatologist in private practice in Boca Raton, Florida, and a clinical affiliate associate professor of dermatology at Florida Atlantic University, Boca Raton.

“There’s not going to be one treatment that’s right for everything,” she said. Different approaches may be required even for the same patient because some people present with all three types of acne scars, she added.

Combining Treatments

When it comes to injecting dermal fillers into acne scars to lift the depressed areas, the US Food and Drug Administration approved a filler with polymethyl methacrylate filler and bovine collagen (Bellafill) for this indication (moderate to severe, atrophic, distensible facial acne scars on the cheek in patients over age 21) in 2015. “And off-label, I use hyaluronic acid in my practice,” Dr. Siperstein said. Each filler “probably works a little bit better or differently on different types of scars.”

For rolling scars, she recommends hyaluronic acid (HA) dermal filler for everyone. “Of course, this is my opinion.” She was also a lead investigator in a randomized, placebo-controlled split-face study comparing HA filler with saline for correcting atrophic facial scars in 15 patients. The HA filler emerged superior, although there were some improvements with saline.

In her clinical experience, patients are happy with the results and ask, “Why didn’t the last four doctors do this?”

Boxcar scars are more challenging to fill with HA. In some cases, Dr. Siperstein is able to raise the depressed portion of the scar, but some of the vertical edges remain. In this scenario, she might combine treatments. Laser resurfacing, for example, might help convert boxcar scars into rolling scars, which then can be filled more successfully.

“Ice pick scars are tough,” Dr. Siperstein said. A punch removal technique can work in some cases, or she might try the “cross technique.” This involves placing acetic acid inside the scar using a Q-tip. “You have to be really careful,” she added, “because if you get it around the edges, it’s actually going to make the scar bigger.”
 

Choosing the Right Candidates

Selecting the right candidate for HA treatment of acne scars is essential. Dr. Siperstein shared the example of a lifeguard who had prominent acne scarring down the center of his chest. “He was embarrassed to go to the beach and take off his shirt. He said he felt like he had bullet holes in his chest.”

One month following treatment, “he had a really nice improvement, and now he feels really comfortable,” she said.

Some dermatologists might be reluctant to consider HA fillers for acne scarring because there is a misconception that HA is short-acting, lasting 6 months to 1 year before the effect wears off. That impression can persist from company-sponsored studies that limit follow-up to 6 months or 1 year “to get their drug to market,” she noted.

Also adding to this impression is that HA fillers in wrinkles may not last as long. Dr. Siperstein explained that wrinkles on the face are dynamic and constantly moving. In contrast, acne scars experience less movement, which helps the HA last longer. There is MRI evidence that shows HA fillers last over 2 years in the face, she added.

One tip to predict how well an acne scar might respond to filler injections is to squeeze it and look for the “dimple sign.” If the floor of the scar lifts up when squeezed, “we know that they’ll be a good candidate for hyaluronic acid filler.” Another tip is to inject HA in a retrograde technique high up in the skin. Inject tiny amounts — microdroplets — of the HA filler high on the dermis, she advised.

Deeper injections run the risk of raising the entire scar instead of filling it, she added.

Like many dermatologic procedures, before and after photos are essential to demonstrate improvements, Dr. Siperstein pointed out. Patients are often skeptical. “This happens a lot with acne scar patients. They’ve been to a million places that have promised results, they have not gotten them, and they are frustrated.”

Acne scars can result from picking, inflammation, or treatment. “This is what we see all day in clinic,” Dr. Siperstein said. “Somebody who had to undergo Accutane treatment but unfortunately is left with holes. This is a huge psychological burden on our patients,” she said, describing a younger patient who had scarring, which “led to depression — it was ruining his life.”

“His mom was willing to do whatever it took. And I said, You know what, I think filler will be enough,” Dr. Siperstein said. She counseled them that treatment would not make the scars disappear completely. But patients used to 10% improvements are very happy when their acne scars look 80% or 90% better, she added.

Dr. Siperstein received grant or research support and is a member of the speakers bureau for Allergan and Galderma. She is also a consultant/advisory board member for Allergan.
 

A version of this article appeared on Medscape.com.

Men with metastatic castration-resistant prostate cancer (mCRPC) that had progressed despite treatment with novel hormonal therapy had a slight but statistically significant improvement in progression-free survival (PFS) with a combination of a targeted agent and immunotherapy compared with a second-line novel hormonal therapy.

The combination of the tyrosine kinase inhibitor (TKI), cabozantinib (Cabometyx), and the immune checkpoint inhibitor (ICI), atezolizumab (Tecentriq), was associated with a median PFS of 6.3 months vs 4.2 months for patients assigned to second hormonal therapy with either abiraterone (Zytiga) and prednisone, or enzalutamide (Xtandi) in the CONTACT-02 trial, Neeraj Agarwal, MD, reported at the ASCO Genitourinary Cancers Symposium. 

“CONTACT 2 is the first phase 3 trial of the TKI/ICI combination to show statistically significant improvement in PFS in patients with mCRPC,” said Dr. Agarwal, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

­­The data support the combination of cabozantinib and atezolizumab as a potential new treatment option for patients with mCRPC that has progressed on novel hormonal therapy, he said.
 

Study Design Questioned

That opinion, however, was not shared by Kim N. Chi, MD, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant.

Dr. Chi acknowledged that the study results as presented were positive, but also pointed to several limitations, including the small difference between the treatment groups in radiographic progression-free survival (rPFS).

“I would say the rPFS benefit is modest, and in the absence of other improvements the difference in the median rPFS is equivalent from one scan to the next in the scanning cycle. I would argue about the clinical significance of that,” he said.

He also noted that there was no improvement in the investigational arm in patient-reported outcomes, and that pain progression and quality-of-life deterioration occurred within 2 to 4 months, which is “quite quick.”

Additionally, he questioned the choice of an androgen receptor pathway inhibitor (ARPI) switch as the control arm of the study.

“I’d also argue that ARPI switch is not the best standard of care for this patient population with measurable disease and 40% visceral metastases; there are better options,” he said.

For example, in phase 3 trials, docetaxel and cabazitaxel (Jevtana) have consistently demonstrated radiographic PFS of 8 to 9 months. In addition, lutetium-177–PSMA-617, a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the tumor microenvironment, has also been shown to have PFS and overall survival benefits, he said.

“Irrespective of regulatory decisions, I personally could not recommend this at this time, given the data that we’ve seen and the better options that are available for this patient population,” Dr. Chi said.
 

Real-World Practice

“Kim Chi offered a pretty fair critique and summary of the control arm, but in real world practice, ARPI switch, from abi [abiraterone] to enza [enzalutamide] or enza to abi continues to be used in routine clinical practice for various reasons,” Xin Gao, MD, a genitourinary oncologist at Mass General Cancer Center in Boston, said in an interview.

“There are patients who can’t tolerate chemotherapy or don’t want chemotherapy, and we do know also that there are patients who can benefit from an ARPI switch, especially some patients with more indolent disease,” said Dr. Gao, who attended the presentation but was not involved in the study.

He noted that some patients being switched from abiraterone to enzalutamide have clinical responses, and that the ARPIs are generally more tolerable than chemotherapy.

In addition, CONTACT-02 is one of a series of trials in which ARPI switch was used as the control arm, and many of these trials were initiated before there were data confirming the superior efficacy of some newer therapeutic options, Dr. Gao noted.

He agreed, however that there is growing evidence to show that ARPI switch may not be the optimal choice for patients with more measurable disease, especially visceral metastases, and other more aggressive forms of mCRPC.
 

CONTACT-02 Details

Investigators in the phase 3 study screened 866 men with mCRPC and after stratification by liver metastases, prior docetaxel use for castration-sensitive prostate cancer, and disease stage for which the first novel hormonal therapy was given. About 500 patients (507) were randomized to receive either oral cabozantinib 40 mg daily plus intravenous atezolizumab 1200 mg every 3 weeks or second hormonal therapy with either abiraterone 1000 mg with oral prednisone 5 mg twice daily, or oral enzalutamide 160 mg daily.

After a median follow-up of 14.3 months in the PFS intention-to-treat population, the median ­PFS by blinded central review was 6.3 months with cabozantinib/atezolizumab and 4.2 months with second hormonal therapy. This translated into a hazard ratio of 0.64 (P = .0002). The results were similar for a PFS analysis according to Prostate Cancer Working Group 3 criteria.

The combination was also associated with modest improvements in PFS in prespecified subgroups, including patients who had liver or bone metastases and those who had previously received docetaxel.

There were no significant differences in overall survival at the time of data cutoff. Overall survival data were not mature and will be reported at a later date.

Disease control rates, a composite of complete and partial responses and stable disease, were 73% with the combination and 55% with second hormonal therapy (P value not shown).
 

Safety Data

The safety analysis indicated that patients found the ARPI switch easier to tolerate than the combination.

Adverse events leading to dose reductions occurred in 40% of patients on the combination, vs 3% of patients on second hormonal therapy, and treatment-related adverse events leading to discontinuation occurred in 13% and 2%, respectively.

Grade 3 or 4 adverse events occurred in 48% of patients assigned to the combination vs. 23% of patients assigned to the ARPI switch.

In all, 8% of patients on the combination and 12% on second hormonal therapy died on study, but none of the deaths were deemed to be treatment related.­­

CONTACT-02 was sponsored by Exelixis in partnerships with Ipsen and Takeda.

Dr. Agarwal disclosed institutional research funding from Exelixis, Roche, Takeda, and others, and travel expenses from Pfizer. Dr. Chi disclosed honoraria, a consulting/advisory role and institutional research funding with Roche and others. Dr. Gao has served as a consultant or advisor to several companies, not including the sponsors of the study, and has served as principal investigator at his institution, which has received research funding from Exelixis, Takeda, and others.

Men with metastatic castration-resistant prostate cancer (mCRPC) that had progressed despite treatment with novel hormonal therapy had a slight but statistically significant improvement in progression-free survival (PFS) with a combination of a targeted agent and immunotherapy compared with a second-line novel hormonal therapy.

The combination of the tyrosine kinase inhibitor (TKI), cabozantinib (Cabometyx), and the immune checkpoint inhibitor (ICI), atezolizumab (Tecentriq), was associated with a median PFS of 6.3 months vs 4.2 months for patients assigned to second hormonal therapy with either abiraterone (Zytiga) and prednisone, or enzalutamide (Xtandi) in the CONTACT-02 trial, Neeraj Agarwal, MD, reported at the ASCO Genitourinary Cancers Symposium. 

“CONTACT 2 is the first phase 3 trial of the TKI/ICI combination to show statistically significant improvement in PFS in patients with mCRPC,” said Dr. Agarwal, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

­­The data support the combination of cabozantinib and atezolizumab as a potential new treatment option for patients with mCRPC that has progressed on novel hormonal therapy, he said.
 

Study Design Questioned

That opinion, however, was not shared by Kim N. Chi, MD, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant.

Dr. Chi acknowledged that the study results as presented were positive, but also pointed to several limitations, including the small difference between the treatment groups in radiographic progression-free survival (rPFS).

“I would say the rPFS benefit is modest, and in the absence of other improvements the difference in the median rPFS is equivalent from one scan to the next in the scanning cycle. I would argue about the clinical significance of that,” he said.

He also noted that there was no improvement in the investigational arm in patient-reported outcomes, and that pain progression and quality-of-life deterioration occurred within 2 to 4 months, which is “quite quick.”

Additionally, he questioned the choice of an androgen receptor pathway inhibitor (ARPI) switch as the control arm of the study.

“I’d also argue that ARPI switch is not the best standard of care for this patient population with measurable disease and 40% visceral metastases; there are better options,” he said.

For example, in phase 3 trials, docetaxel and cabazitaxel (Jevtana) have consistently demonstrated radiographic PFS of 8 to 9 months. In addition, lutetium-177–PSMA-617, a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the tumor microenvironment, has also been shown to have PFS and overall survival benefits, he said.

“Irrespective of regulatory decisions, I personally could not recommend this at this time, given the data that we’ve seen and the better options that are available for this patient population,” Dr. Chi said.
 

Real-World Practice

“Kim Chi offered a pretty fair critique and summary of the control arm, but in real world practice, ARPI switch, from abi [abiraterone] to enza [enzalutamide] or enza to abi continues to be used in routine clinical practice for various reasons,” Xin Gao, MD, a genitourinary oncologist at Mass General Cancer Center in Boston, said in an interview.

“There are patients who can’t tolerate chemotherapy or don’t want chemotherapy, and we do know also that there are patients who can benefit from an ARPI switch, especially some patients with more indolent disease,” said Dr. Gao, who attended the presentation but was not involved in the study.

He noted that some patients being switched from abiraterone to enzalutamide have clinical responses, and that the ARPIs are generally more tolerable than chemotherapy.

In addition, CONTACT-02 is one of a series of trials in which ARPI switch was used as the control arm, and many of these trials were initiated before there were data confirming the superior efficacy of some newer therapeutic options, Dr. Gao noted.

He agreed, however that there is growing evidence to show that ARPI switch may not be the optimal choice for patients with more measurable disease, especially visceral metastases, and other more aggressive forms of mCRPC.
 

CONTACT-02 Details

Investigators in the phase 3 study screened 866 men with mCRPC and after stratification by liver metastases, prior docetaxel use for castration-sensitive prostate cancer, and disease stage for which the first novel hormonal therapy was given. About 500 patients (507) were randomized to receive either oral cabozantinib 40 mg daily plus intravenous atezolizumab 1200 mg every 3 weeks or second hormonal therapy with either abiraterone 1000 mg with oral prednisone 5 mg twice daily, or oral enzalutamide 160 mg daily.

After a median follow-up of 14.3 months in the PFS intention-to-treat population, the median ­PFS by blinded central review was 6.3 months with cabozantinib/atezolizumab and 4.2 months with second hormonal therapy. This translated into a hazard ratio of 0.64 (P = .0002). The results were similar for a PFS analysis according to Prostate Cancer Working Group 3 criteria.

The combination was also associated with modest improvements in PFS in prespecified subgroups, including patients who had liver or bone metastases and those who had previously received docetaxel.

There were no significant differences in overall survival at the time of data cutoff. Overall survival data were not mature and will be reported at a later date.

Disease control rates, a composite of complete and partial responses and stable disease, were 73% with the combination and 55% with second hormonal therapy (P value not shown).
 

Safety Data

The safety analysis indicated that patients found the ARPI switch easier to tolerate than the combination.

Adverse events leading to dose reductions occurred in 40% of patients on the combination, vs 3% of patients on second hormonal therapy, and treatment-related adverse events leading to discontinuation occurred in 13% and 2%, respectively.

Grade 3 or 4 adverse events occurred in 48% of patients assigned to the combination vs. 23% of patients assigned to the ARPI switch.

In all, 8% of patients on the combination and 12% on second hormonal therapy died on study, but none of the deaths were deemed to be treatment related.­­

CONTACT-02 was sponsored by Exelixis in partnerships with Ipsen and Takeda.

Dr. Agarwal disclosed institutional research funding from Exelixis, Roche, Takeda, and others, and travel expenses from Pfizer. Dr. Chi disclosed honoraria, a consulting/advisory role and institutional research funding with Roche and others. Dr. Gao has served as a consultant or advisor to several companies, not including the sponsors of the study, and has served as principal investigator at his institution, which has received research funding from Exelixis, Takeda, and others.

Men with metastatic castration-resistant prostate cancer (mCRPC) that had progressed despite treatment with novel hormonal therapy had a slight but statistically significant improvement in progression-free survival (PFS) with a combination of a targeted agent and immunotherapy compared with a second-line novel hormonal therapy.

The combination of the tyrosine kinase inhibitor (TKI), cabozantinib (Cabometyx), and the immune checkpoint inhibitor (ICI), atezolizumab (Tecentriq), was associated with a median PFS of 6.3 months vs 4.2 months for patients assigned to second hormonal therapy with either abiraterone (Zytiga) and prednisone, or enzalutamide (Xtandi) in the CONTACT-02 trial, Neeraj Agarwal, MD, reported at the ASCO Genitourinary Cancers Symposium. 

“CONTACT 2 is the first phase 3 trial of the TKI/ICI combination to show statistically significant improvement in PFS in patients with mCRPC,” said Dr. Agarwal, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

­­The data support the combination of cabozantinib and atezolizumab as a potential new treatment option for patients with mCRPC that has progressed on novel hormonal therapy, he said.
 

Study Design Questioned

That opinion, however, was not shared by Kim N. Chi, MD, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant.

Dr. Chi acknowledged that the study results as presented were positive, but also pointed to several limitations, including the small difference between the treatment groups in radiographic progression-free survival (rPFS).

“I would say the rPFS benefit is modest, and in the absence of other improvements the difference in the median rPFS is equivalent from one scan to the next in the scanning cycle. I would argue about the clinical significance of that,” he said.

He also noted that there was no improvement in the investigational arm in patient-reported outcomes, and that pain progression and quality-of-life deterioration occurred within 2 to 4 months, which is “quite quick.”

Additionally, he questioned the choice of an androgen receptor pathway inhibitor (ARPI) switch as the control arm of the study.

“I’d also argue that ARPI switch is not the best standard of care for this patient population with measurable disease and 40% visceral metastases; there are better options,” he said.

For example, in phase 3 trials, docetaxel and cabazitaxel (Jevtana) have consistently demonstrated radiographic PFS of 8 to 9 months. In addition, lutetium-177–PSMA-617, a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the tumor microenvironment, has also been shown to have PFS and overall survival benefits, he said.

“Irrespective of regulatory decisions, I personally could not recommend this at this time, given the data that we’ve seen and the better options that are available for this patient population,” Dr. Chi said.
 

Real-World Practice

“Kim Chi offered a pretty fair critique and summary of the control arm, but in real world practice, ARPI switch, from abi [abiraterone] to enza [enzalutamide] or enza to abi continues to be used in routine clinical practice for various reasons,” Xin Gao, MD, a genitourinary oncologist at Mass General Cancer Center in Boston, said in an interview.

“There are patients who can’t tolerate chemotherapy or don’t want chemotherapy, and we do know also that there are patients who can benefit from an ARPI switch, especially some patients with more indolent disease,” said Dr. Gao, who attended the presentation but was not involved in the study.

He noted that some patients being switched from abiraterone to enzalutamide have clinical responses, and that the ARPIs are generally more tolerable than chemotherapy.

In addition, CONTACT-02 is one of a series of trials in which ARPI switch was used as the control arm, and many of these trials were initiated before there were data confirming the superior efficacy of some newer therapeutic options, Dr. Gao noted.

He agreed, however that there is growing evidence to show that ARPI switch may not be the optimal choice for patients with more measurable disease, especially visceral metastases, and other more aggressive forms of mCRPC.
 

CONTACT-02 Details

Investigators in the phase 3 study screened 866 men with mCRPC and after stratification by liver metastases, prior docetaxel use for castration-sensitive prostate cancer, and disease stage for which the first novel hormonal therapy was given. About 500 patients (507) were randomized to receive either oral cabozantinib 40 mg daily plus intravenous atezolizumab 1200 mg every 3 weeks or second hormonal therapy with either abiraterone 1000 mg with oral prednisone 5 mg twice daily, or oral enzalutamide 160 mg daily.

After a median follow-up of 14.3 months in the PFS intention-to-treat population, the median ­PFS by blinded central review was 6.3 months with cabozantinib/atezolizumab and 4.2 months with second hormonal therapy. This translated into a hazard ratio of 0.64 (P = .0002). The results were similar for a PFS analysis according to Prostate Cancer Working Group 3 criteria.

The combination was also associated with modest improvements in PFS in prespecified subgroups, including patients who had liver or bone metastases and those who had previously received docetaxel.

There were no significant differences in overall survival at the time of data cutoff. Overall survival data were not mature and will be reported at a later date.

Disease control rates, a composite of complete and partial responses and stable disease, were 73% with the combination and 55% with second hormonal therapy (P value not shown).
 

Safety Data

The safety analysis indicated that patients found the ARPI switch easier to tolerate than the combination.

Adverse events leading to dose reductions occurred in 40% of patients on the combination, vs 3% of patients on second hormonal therapy, and treatment-related adverse events leading to discontinuation occurred in 13% and 2%, respectively.

Grade 3 or 4 adverse events occurred in 48% of patients assigned to the combination vs. 23% of patients assigned to the ARPI switch.

In all, 8% of patients on the combination and 12% on second hormonal therapy died on study, but none of the deaths were deemed to be treatment related.­­

CONTACT-02 was sponsored by Exelixis in partnerships with Ipsen and Takeda.

Dr. Agarwal disclosed institutional research funding from Exelixis, Roche, Takeda, and others, and travel expenses from Pfizer. Dr. Chi disclosed honoraria, a consulting/advisory role and institutional research funding with Roche and others. Dr. Gao has served as a consultant or advisor to several companies, not including the sponsors of the study, and has served as principal investigator at his institution, which has received research funding from Exelixis, Takeda, and others.

Two drugs delivered in combination are better than one after the other for the first-line treatment of men with metastatic castration-resistant prostate cancer bearing homologous recombination-repair mutations.

That’s the conclusion of investigators in the phase 2 BRCAAway trial, which compared a combination of abiraterone (Zytiga) and prednisone plus olaparib (Lynparza) against sequential therapy with the same agents.

At the time of data cutoff, median progression-free survival (PFS), the primary endpoint, was 39 months for patients randomized to the combination, compared with 8.4 months for those assigned to abiraterone/prednisone, and 14 months for those assigned to olaparib monotherapy, reported Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center in Chicago.

“In patients with metastatic castration-resistant prostate cancer [mCRPC] and BRCA1/2 or ATM alterations, abiraterone and prednisone plus olaparib was well tolerated and resulted in better progression-free survival and response rates vs. single-agent olaparib or abiraterone/prednisone,” she said in an oral abstract presentation at the ASCO Genitourinary Cancers Symposium.

Although the study allowed crossover between the single-agent arms at the time of progression, only a few patients made the switch. Nonetheless, in these patients the PFS with the frontline combination was superior to that of sequential therapy, she noted.
 

Study Rationale and Design

Germline or somatic mutations in genes encoding for homologous recombination-repair occur in about 20% of men with mCRPC. Olaparib, a PARP1 (poly-adp ribose polymerase-1) inhibitor, interacts with androgen signaling, and preclinical studies have shown that castration-resistant prostate tumor cells have increased PARP1 activity. In addition, PARP1 has been shown preclinically to synergize with androgen receptor pathway inhibitors (ARPIs) such as abiraterone, Dr. Hussain explained.

The BRCAAway trial was designed to test whether co-targeting the androgen receptor and PARP1 could result in higher and more durable responses than current frontline therapies in patients with mCRPC with DNA-damage response mutations.

Patients with mCRPC with no prior exposure to either a PARP1 inhibitor, androgen receptor inhibitor, or mCRPC-directed chemotherapy underwent next-generation sequencing and germline testing of tumor tissues, and those patients found to have inactivating BRCA1/2 and/or ATM alterations were randomized on a 1:1:1 basis to either abiraterone 1000 mg daily plus prednisone 5 mg twice daily (19 patients); olaparib 300 mg twice daily (21 patients); or to the combination (21 patients).

The primary endpoint was radiographic PFS according to RECIST 1.1 criteria, Prostate Cancer Working Group 3 criteria, clinical assessment, or death.

As noted, the median PFS was 8.4 months with abiraterone/prednisone, 14 months with olaparib, and 39 months with the combination.

Secondary endpoints also favored the combination therapy arm, with objective response rates of 22%, 14%, and 33%, respectively; PSA response rates of 61%, 67% and 95%; and undetectable PSA response rates of 17%, 14%, and 33%.

A total of 8 of 19 patients on abiraterone were crossed over to olaparib, and 8 of 21 initially assigned to olaparib were crossed over to abiraterone. In these patients the median PFS from crossover was 8.3 and 7.2 months, respectively. In each crossover group the median PFS from the time of randomization was 16 months.

There were no grade 4 adverse events or treatment-related deaths reported in any of the study arms, and “essentially when you look at the adverse events, they pretty much are consistent with what you would expect to see with these particular agents,” Dr. Hussain said.

“Overall the patients were tolerating the treatment well,” she added.
 

Practice Changing with Caveats

Kim N. Chi, MD, FRCPC, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant, said that the strengths of the study included an olaparib monotherapy arm — something that was missing from phase 3 trials — that provides insights into how PARP inhibitors perform in this population. He also applauded the inclusion of clinical assessment as a primary endpoint, noting that “this is what we do in routine practice, and therefore, the generalizability of the trial becomes more evident.”

The crossover design provides important information about whether an upfront combination or a sequential therapy approach is more effective, as well, he added.

He pointed out, however, that the trial was limited by small sample size and by its “horse race” design rather than as a comparison trial.

“So how does the BRCAAway trial change our practice? Despite the limitations, I think it does support an upfront PARP inhibitor-ARPI combination as firstline therapy for HRR gene-mutated metastatic CRPC. These data suggest synergy, and most importantly, there is no loss of opportunity [for more effective therapies]. However, the limitations of the trial will not end this debate today,” he said.

The trial was funded by AstraZeneca. Both Dr. Hussain and Dr. Chi disclosed honoraria, consulting/advising, and institutional research funding from AstraZeneca and others.

Two drugs delivered in combination are better than one after the other for the first-line treatment of men with metastatic castration-resistant prostate cancer bearing homologous recombination-repair mutations.

That’s the conclusion of investigators in the phase 2 BRCAAway trial, which compared a combination of abiraterone (Zytiga) and prednisone plus olaparib (Lynparza) against sequential therapy with the same agents.

At the time of data cutoff, median progression-free survival (PFS), the primary endpoint, was 39 months for patients randomized to the combination, compared with 8.4 months for those assigned to abiraterone/prednisone, and 14 months for those assigned to olaparib monotherapy, reported Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center in Chicago.

“In patients with metastatic castration-resistant prostate cancer [mCRPC] and BRCA1/2 or ATM alterations, abiraterone and prednisone plus olaparib was well tolerated and resulted in better progression-free survival and response rates vs. single-agent olaparib or abiraterone/prednisone,” she said in an oral abstract presentation at the ASCO Genitourinary Cancers Symposium.

Although the study allowed crossover between the single-agent arms at the time of progression, only a few patients made the switch. Nonetheless, in these patients the PFS with the frontline combination was superior to that of sequential therapy, she noted.
 

Study Rationale and Design

Germline or somatic mutations in genes encoding for homologous recombination-repair occur in about 20% of men with mCRPC. Olaparib, a PARP1 (poly-adp ribose polymerase-1) inhibitor, interacts with androgen signaling, and preclinical studies have shown that castration-resistant prostate tumor cells have increased PARP1 activity. In addition, PARP1 has been shown preclinically to synergize with androgen receptor pathway inhibitors (ARPIs) such as abiraterone, Dr. Hussain explained.

The BRCAAway trial was designed to test whether co-targeting the androgen receptor and PARP1 could result in higher and more durable responses than current frontline therapies in patients with mCRPC with DNA-damage response mutations.

Patients with mCRPC with no prior exposure to either a PARP1 inhibitor, androgen receptor inhibitor, or mCRPC-directed chemotherapy underwent next-generation sequencing and germline testing of tumor tissues, and those patients found to have inactivating BRCA1/2 and/or ATM alterations were randomized on a 1:1:1 basis to either abiraterone 1000 mg daily plus prednisone 5 mg twice daily (19 patients); olaparib 300 mg twice daily (21 patients); or to the combination (21 patients).

The primary endpoint was radiographic PFS according to RECIST 1.1 criteria, Prostate Cancer Working Group 3 criteria, clinical assessment, or death.

As noted, the median PFS was 8.4 months with abiraterone/prednisone, 14 months with olaparib, and 39 months with the combination.

Secondary endpoints also favored the combination therapy arm, with objective response rates of 22%, 14%, and 33%, respectively; PSA response rates of 61%, 67% and 95%; and undetectable PSA response rates of 17%, 14%, and 33%.

A total of 8 of 19 patients on abiraterone were crossed over to olaparib, and 8 of 21 initially assigned to olaparib were crossed over to abiraterone. In these patients the median PFS from crossover was 8.3 and 7.2 months, respectively. In each crossover group the median PFS from the time of randomization was 16 months.

There were no grade 4 adverse events or treatment-related deaths reported in any of the study arms, and “essentially when you look at the adverse events, they pretty much are consistent with what you would expect to see with these particular agents,” Dr. Hussain said.

“Overall the patients were tolerating the treatment well,” she added.
 

Practice Changing with Caveats

Kim N. Chi, MD, FRCPC, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant, said that the strengths of the study included an olaparib monotherapy arm — something that was missing from phase 3 trials — that provides insights into how PARP inhibitors perform in this population. He also applauded the inclusion of clinical assessment as a primary endpoint, noting that “this is what we do in routine practice, and therefore, the generalizability of the trial becomes more evident.”

The crossover design provides important information about whether an upfront combination or a sequential therapy approach is more effective, as well, he added.

He pointed out, however, that the trial was limited by small sample size and by its “horse race” design rather than as a comparison trial.

“So how does the BRCAAway trial change our practice? Despite the limitations, I think it does support an upfront PARP inhibitor-ARPI combination as firstline therapy for HRR gene-mutated metastatic CRPC. These data suggest synergy, and most importantly, there is no loss of opportunity [for more effective therapies]. However, the limitations of the trial will not end this debate today,” he said.

The trial was funded by AstraZeneca. Both Dr. Hussain and Dr. Chi disclosed honoraria, consulting/advising, and institutional research funding from AstraZeneca and others.

Two drugs delivered in combination are better than one after the other for the first-line treatment of men with metastatic castration-resistant prostate cancer bearing homologous recombination-repair mutations.

That’s the conclusion of investigators in the phase 2 BRCAAway trial, which compared a combination of abiraterone (Zytiga) and prednisone plus olaparib (Lynparza) against sequential therapy with the same agents.

At the time of data cutoff, median progression-free survival (PFS), the primary endpoint, was 39 months for patients randomized to the combination, compared with 8.4 months for those assigned to abiraterone/prednisone, and 14 months for those assigned to olaparib monotherapy, reported Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center in Chicago.

“In patients with metastatic castration-resistant prostate cancer [mCRPC] and BRCA1/2 or ATM alterations, abiraterone and prednisone plus olaparib was well tolerated and resulted in better progression-free survival and response rates vs. single-agent olaparib or abiraterone/prednisone,” she said in an oral abstract presentation at the ASCO Genitourinary Cancers Symposium.

Although the study allowed crossover between the single-agent arms at the time of progression, only a few patients made the switch. Nonetheless, in these patients the PFS with the frontline combination was superior to that of sequential therapy, she noted.
 

Study Rationale and Design

Germline or somatic mutations in genes encoding for homologous recombination-repair occur in about 20% of men with mCRPC. Olaparib, a PARP1 (poly-adp ribose polymerase-1) inhibitor, interacts with androgen signaling, and preclinical studies have shown that castration-resistant prostate tumor cells have increased PARP1 activity. In addition, PARP1 has been shown preclinically to synergize with androgen receptor pathway inhibitors (ARPIs) such as abiraterone, Dr. Hussain explained.

The BRCAAway trial was designed to test whether co-targeting the androgen receptor and PARP1 could result in higher and more durable responses than current frontline therapies in patients with mCRPC with DNA-damage response mutations.

Patients with mCRPC with no prior exposure to either a PARP1 inhibitor, androgen receptor inhibitor, or mCRPC-directed chemotherapy underwent next-generation sequencing and germline testing of tumor tissues, and those patients found to have inactivating BRCA1/2 and/or ATM alterations were randomized on a 1:1:1 basis to either abiraterone 1000 mg daily plus prednisone 5 mg twice daily (19 patients); olaparib 300 mg twice daily (21 patients); or to the combination (21 patients).

The primary endpoint was radiographic PFS according to RECIST 1.1 criteria, Prostate Cancer Working Group 3 criteria, clinical assessment, or death.

As noted, the median PFS was 8.4 months with abiraterone/prednisone, 14 months with olaparib, and 39 months with the combination.

Secondary endpoints also favored the combination therapy arm, with objective response rates of 22%, 14%, and 33%, respectively; PSA response rates of 61%, 67% and 95%; and undetectable PSA response rates of 17%, 14%, and 33%.

A total of 8 of 19 patients on abiraterone were crossed over to olaparib, and 8 of 21 initially assigned to olaparib were crossed over to abiraterone. In these patients the median PFS from crossover was 8.3 and 7.2 months, respectively. In each crossover group the median PFS from the time of randomization was 16 months.

There were no grade 4 adverse events or treatment-related deaths reported in any of the study arms, and “essentially when you look at the adverse events, they pretty much are consistent with what you would expect to see with these particular agents,” Dr. Hussain said.

“Overall the patients were tolerating the treatment well,” she added.
 

Practice Changing with Caveats

Kim N. Chi, MD, FRCPC, of the University of British Columbia in Vancouver, BC, Canada, the invited discussant, said that the strengths of the study included an olaparib monotherapy arm — something that was missing from phase 3 trials — that provides insights into how PARP inhibitors perform in this population. He also applauded the inclusion of clinical assessment as a primary endpoint, noting that “this is what we do in routine practice, and therefore, the generalizability of the trial becomes more evident.”

The crossover design provides important information about whether an upfront combination or a sequential therapy approach is more effective, as well, he added.

He pointed out, however, that the trial was limited by small sample size and by its “horse race” design rather than as a comparison trial.

“So how does the BRCAAway trial change our practice? Despite the limitations, I think it does support an upfront PARP inhibitor-ARPI combination as firstline therapy for HRR gene-mutated metastatic CRPC. These data suggest synergy, and most importantly, there is no loss of opportunity [for more effective therapies]. However, the limitations of the trial will not end this debate today,” he said.

The trial was funded by AstraZeneca. Both Dr. Hussain and Dr. Chi disclosed honoraria, consulting/advising, and institutional research funding from AstraZeneca and others.

LAS VEGAS — In patients with inflammatory bowel disease (IBD), measurement of microbial cell-free DNA (cfDNA) in plasma may help distinguish active from asymptomatic disease, as well as between ulcerative colitis and Crohn’s disease.

“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.

cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.

Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.

The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.

cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.

The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
 

An ‘Intriguing’ Method

During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.

Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.

“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.

Weill Cornell Medical College

He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.

He also called for prospective studies to validate the approach.

If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.

Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..

LAS VEGAS — In patients with inflammatory bowel disease (IBD), measurement of microbial cell-free DNA (cfDNA) in plasma may help distinguish active from asymptomatic disease, as well as between ulcerative colitis and Crohn’s disease.

“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.

cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.

Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.

The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.

cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.

The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
 

An ‘Intriguing’ Method

During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.

Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.

“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.

Weill Cornell Medical College

He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.

He also called for prospective studies to validate the approach.

If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.

Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..

LAS VEGAS — In patients with inflammatory bowel disease (IBD), measurement of microbial cell-free DNA (cfDNA) in plasma may help distinguish active from asymptomatic disease, as well as between ulcerative colitis and Crohn’s disease.

“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.

cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.

Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.

The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.

cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.

The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
 

An ‘Intriguing’ Method

During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.

Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.

“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.

Weill Cornell Medical College

He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.

He also called for prospective studies to validate the approach.

If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.

Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..

CHICAGO — The top facial concerns in Asian women relate to uneven skin color, hyperpigmentation, hair thinning, and under-eye dark circles, according to a study presented at the annual meeting of the American Society for Dermatologic Surgery (ASDS),

“Asian Americans represent the fastest-expanding racial group in the US, underscoring the need for a comprehensive understanding of their specific aesthetic goals and needs,” said Annie Chiu, MD, a cosmetic dermatologist in Redondo Beach, California, who presented the results at the meeting. In an interview, she noted that most of this type of research has been done in White or Eurocentric populations, “so we really wanted to identify the top aesthetic concerns for Asian women as they tend to be different.”

In the study, an online survey was administered to aesthetically-inclined adults — defined as those who care about improving their appearance and are willing to go to a professional to do so — across different demographic groups in the United States. Respondents were surveyed about 41 facial and 31 body characteristics, identifying those they have and find bothersome. Maximum difference scaling was used to generate their most and least bothersome characteristics in each respective category.

Of the 3,974 women surveyed, 652 self-identified as female and Asian. The majority of Asian female respondents self-reported a Fitzpatrick skin type IV (East/Southeast [SE]Asian: 58%; Indian/Central or Southwest [CSW] Asian: 24%) or type V (East/SE Asian: 59%; Indian/CSW Asian: 30%). The findings reported at the meeting are specific to aesthetic concerns in Asian women.

Among the Asian female participants, the top three facial concerns were uneven skin color (40%), dull/dry skin (35%), and hair loss/thinning (34%). Top facial concerns in younger patients (under 30 years) were related to skin quality, such as dull skin (54%), acne scarring (51%), and large pore size (51%), whereas the most common concerns among those older than 57 years were related to under-eye bags or sagginess (60%), uneven skin tone (55%), and hair loss/thinning (47%).

Of note, acne scarring was noted as a top concern by the Indian/CSW Asian cohort. While the lines between the brows and skin sagging were top concerns in White female participants in the overall study, these concerns were not nearly as high among Asian female participants.

For all Asian female participants, the top body concerns were related to stubborn body fat in the stomach, sides, bra or back area, and arms. Stubborn body fat in the stomach area was the most frequent concern across generations (41% to 64%). East/SE Asian participants were more interested in receiving cosmetic treatments (91%) than the Indian/CSW Asian group (47%).

“Given that injectable treatments of neuromodulators and fillers are often what we focus aesthetic treatments around and thus, what we often center cosmetic consults on, it is important to remember to customize patient consultations and address specific needs with cultural sensitivity,” Dr. Chiu said. “We may not be properly recognizing and prioritizing patient discussion around concerns of dyspigmentation, skin quality, or hair thinning,” she continued, adding: “Ultimately as experts, it’s important we use this data along with what we know about structural and cutaneous differences in patients of different cultural backgrounds to optimize and prioritize treatments.”

Allergan Aesthetics, an AbbVie company, funded the study and participated in the trial design, research, analysis, data collection, interpretation of data, and the review. Dr. Chiu is a consultant, advisory board member, and investigator for Allergan, AbbVie,and Merz; and is a consultant and advisory board member for Galderma, Evolus, and Sofwave. Other authors disclosed ties with Allergan, Merz Aesthetics, Prollenium, Revance, Galderma, Alastin, Glo Pharma, and Teoxane. Two authors are AbbVie employees.

CHICAGO — The top facial concerns in Asian women relate to uneven skin color, hyperpigmentation, hair thinning, and under-eye dark circles, according to a study presented at the annual meeting of the American Society for Dermatologic Surgery (ASDS),

“Asian Americans represent the fastest-expanding racial group in the US, underscoring the need for a comprehensive understanding of their specific aesthetic goals and needs,” said Annie Chiu, MD, a cosmetic dermatologist in Redondo Beach, California, who presented the results at the meeting. In an interview, she noted that most of this type of research has been done in White or Eurocentric populations, “so we really wanted to identify the top aesthetic concerns for Asian women as they tend to be different.”

In the study, an online survey was administered to aesthetically-inclined adults — defined as those who care about improving their appearance and are willing to go to a professional to do so — across different demographic groups in the United States. Respondents were surveyed about 41 facial and 31 body characteristics, identifying those they have and find bothersome. Maximum difference scaling was used to generate their most and least bothersome characteristics in each respective category.

Of the 3,974 women surveyed, 652 self-identified as female and Asian. The majority of Asian female respondents self-reported a Fitzpatrick skin type IV (East/Southeast [SE]Asian: 58%; Indian/Central or Southwest [CSW] Asian: 24%) or type V (East/SE Asian: 59%; Indian/CSW Asian: 30%). The findings reported at the meeting are specific to aesthetic concerns in Asian women.

Among the Asian female participants, the top three facial concerns were uneven skin color (40%), dull/dry skin (35%), and hair loss/thinning (34%). Top facial concerns in younger patients (under 30 years) were related to skin quality, such as dull skin (54%), acne scarring (51%), and large pore size (51%), whereas the most common concerns among those older than 57 years were related to under-eye bags or sagginess (60%), uneven skin tone (55%), and hair loss/thinning (47%).

Of note, acne scarring was noted as a top concern by the Indian/CSW Asian cohort. While the lines between the brows and skin sagging were top concerns in White female participants in the overall study, these concerns were not nearly as high among Asian female participants.

For all Asian female participants, the top body concerns were related to stubborn body fat in the stomach, sides, bra or back area, and arms. Stubborn body fat in the stomach area was the most frequent concern across generations (41% to 64%). East/SE Asian participants were more interested in receiving cosmetic treatments (91%) than the Indian/CSW Asian group (47%).

“Given that injectable treatments of neuromodulators and fillers are often what we focus aesthetic treatments around and thus, what we often center cosmetic consults on, it is important to remember to customize patient consultations and address specific needs with cultural sensitivity,” Dr. Chiu said. “We may not be properly recognizing and prioritizing patient discussion around concerns of dyspigmentation, skin quality, or hair thinning,” she continued, adding: “Ultimately as experts, it’s important we use this data along with what we know about structural and cutaneous differences in patients of different cultural backgrounds to optimize and prioritize treatments.”

Allergan Aesthetics, an AbbVie company, funded the study and participated in the trial design, research, analysis, data collection, interpretation of data, and the review. Dr. Chiu is a consultant, advisory board member, and investigator for Allergan, AbbVie,and Merz; and is a consultant and advisory board member for Galderma, Evolus, and Sofwave. Other authors disclosed ties with Allergan, Merz Aesthetics, Prollenium, Revance, Galderma, Alastin, Glo Pharma, and Teoxane. Two authors are AbbVie employees.

CHICAGO — The top facial concerns in Asian women relate to uneven skin color, hyperpigmentation, hair thinning, and under-eye dark circles, according to a study presented at the annual meeting of the American Society for Dermatologic Surgery (ASDS),

“Asian Americans represent the fastest-expanding racial group in the US, underscoring the need for a comprehensive understanding of their specific aesthetic goals and needs,” said Annie Chiu, MD, a cosmetic dermatologist in Redondo Beach, California, who presented the results at the meeting. In an interview, she noted that most of this type of research has been done in White or Eurocentric populations, “so we really wanted to identify the top aesthetic concerns for Asian women as they tend to be different.”

In the study, an online survey was administered to aesthetically-inclined adults — defined as those who care about improving their appearance and are willing to go to a professional to do so — across different demographic groups in the United States. Respondents were surveyed about 41 facial and 31 body characteristics, identifying those they have and find bothersome. Maximum difference scaling was used to generate their most and least bothersome characteristics in each respective category.

Of the 3,974 women surveyed, 652 self-identified as female and Asian. The majority of Asian female respondents self-reported a Fitzpatrick skin type IV (East/Southeast [SE]Asian: 58%; Indian/Central or Southwest [CSW] Asian: 24%) or type V (East/SE Asian: 59%; Indian/CSW Asian: 30%). The findings reported at the meeting are specific to aesthetic concerns in Asian women.

Among the Asian female participants, the top three facial concerns were uneven skin color (40%), dull/dry skin (35%), and hair loss/thinning (34%). Top facial concerns in younger patients (under 30 years) were related to skin quality, such as dull skin (54%), acne scarring (51%), and large pore size (51%), whereas the most common concerns among those older than 57 years were related to under-eye bags or sagginess (60%), uneven skin tone (55%), and hair loss/thinning (47%).

Of note, acne scarring was noted as a top concern by the Indian/CSW Asian cohort. While the lines between the brows and skin sagging were top concerns in White female participants in the overall study, these concerns were not nearly as high among Asian female participants.

For all Asian female participants, the top body concerns were related to stubborn body fat in the stomach, sides, bra or back area, and arms. Stubborn body fat in the stomach area was the most frequent concern across generations (41% to 64%). East/SE Asian participants were more interested in receiving cosmetic treatments (91%) than the Indian/CSW Asian group (47%).

“Given that injectable treatments of neuromodulators and fillers are often what we focus aesthetic treatments around and thus, what we often center cosmetic consults on, it is important to remember to customize patient consultations and address specific needs with cultural sensitivity,” Dr. Chiu said. “We may not be properly recognizing and prioritizing patient discussion around concerns of dyspigmentation, skin quality, or hair thinning,” she continued, adding: “Ultimately as experts, it’s important we use this data along with what we know about structural and cutaneous differences in patients of different cultural backgrounds to optimize and prioritize treatments.”

Allergan Aesthetics, an AbbVie company, funded the study and participated in the trial design, research, analysis, data collection, interpretation of data, and the review. Dr. Chiu is a consultant, advisory board member, and investigator for Allergan, AbbVie,and Merz; and is a consultant and advisory board member for Galderma, Evolus, and Sofwave. Other authors disclosed ties with Allergan, Merz Aesthetics, Prollenium, Revance, Galderma, Alastin, Glo Pharma, and Teoxane. Two authors are AbbVie employees.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients. That improved accuracy was observed across diverse racial and ethnic groups, in a new study.

“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.

While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.

Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.

The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.

The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.

Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.

Study Methods and Results

To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.

Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.

Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.

Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.

Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.

In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).

Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.

Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.

Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.
 

Stockholm3 Expected to be Available in U.S. This Year

The test, which has been available in Sweden since 2018, is expected to become commercially available in the United States in early 2024. Dr. Eggener noted that “cost of the test hasn’t been finalized, but will be considerably more expensive than PSA, which is very cheap.”

Commenting on the findings, Bradley McGregor, MD, of the Dana Farber Cancer Institute and an ASCO oncology expert, noted that “ultimately, the goal [of prostate screening] is to be able to better decide when a biopsy is going to yield a clinically relevant prostate cancer, [and] this study gives us some insight of the use of the Stockholm3 tool in a more diverse population.

“How the tool will be utilized in the clinic and in guidelines is something that is a work in progress,” he added. “But I think this provides some reassurances that this will have implications beyond just the homogeneous populations in the original studies.”

Dr. McGregor noted that considerations of the issue of cost should be weighed against the potential costs involved in unnecessary biopsies and a host of other costs that can arise with an inaccurate risk assessment.

“If there is a way to avoid those costs and help us have more confidence in the prostate test results and intervene at an earlier stage, I think that’s exciting,” he said.

Dr. Eggener has consulted for A3P Biomedical but had no financial relationship with the company to disclose.

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

LAS VEGAS — Measuring disease status in inflammatory bowel disease (IBD) patients generally requires invasive blood draws or procedures, but a novel wearable device shows initial promise at providing similar information from perspiration.

The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.

Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.

University of Texas at Dallas

The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.

The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.

The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.

The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.

A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.

The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.

The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.

There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.

Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
 

Treating to Target

The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.

He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.

If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.

Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.

The ulcerative colitis drug etrasimod (Velsipity, Pfizer) appears to be efficacious in eosinophilic esophagitis (EoE), with notable reductions seen in eosinophils.

Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.

“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.

Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
 

VOYAGE Study

In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.

The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.

After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.

Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.

Meanwhile, there was a 61% increase in PEC for people who were given placebo.

Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:

• Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
• Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.

Higher Dose Arm, Better Results

In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”

The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.

“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”

Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.

In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.

Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
 

Prospect of Another EoE Treatment

In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”

The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.

“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.

The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.

“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”

In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.

“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.

Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.

The ulcerative colitis drug etrasimod (Velsipity, Pfizer) appears to be efficacious in eosinophilic esophagitis (EoE), with notable reductions seen in eosinophils.

Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.

“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.

Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
 

VOYAGE Study

In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.

The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.

After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.

Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.

Meanwhile, there was a 61% increase in PEC for people who were given placebo.

Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:

• Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
• Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.

Higher Dose Arm, Better Results

In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”

The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.

“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”

Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.

In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.

Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
 

Prospect of Another EoE Treatment

In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”

The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.

“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.

The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.

“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”

In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.

“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.

Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.

The ulcerative colitis drug etrasimod (Velsipity, Pfizer) appears to be efficacious in eosinophilic esophagitis (EoE), with notable reductions seen in eosinophils.

Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.

“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.

Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
 

VOYAGE Study

In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.

The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.

After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.

Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.

Meanwhile, there was a 61% increase in PEC for people who were given placebo.

Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:

• Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
• Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.

Higher Dose Arm, Better Results

In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”

The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.

“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”

Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.

In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.

Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
 

Prospect of Another EoE Treatment

In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”

The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.

“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.

The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.

“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”

In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.

“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.

Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.