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Top AGA Community patient cases
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org/discussions) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses.
In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Perianal fistula found in UC patient (http://ow.ly/S8bJ30okWuO)
A 20-year-old male patient with no previous medical history was seen and treated last year for pancolitis. His physician solicits drug therapy preferences from the GI community, given the age of the patient and a newly discovered perianal fistula.
2. IBD patient with risk of cancer (http://ow.ly/KoGz30oHdjG)
A 62-year-old female patient with a long history of Crohn’s disease developed acute hepatitis. She had a colectomy in 2011 where a one-stage ileo rectal anastomosis was performed instead of a J-pouch. She was in remission under surveillance and mesalamine, until recently. She also has primary sclerosing cholangitis (PSC) and multifocal dysplasia, a combination that raised concern among the GI community about the patient’s risk of cancer.
3. Significant daily pain in Crohn’s patient (http://ow.ly/FHUI30oHdI8)
A recent colonoscopy for a 39-year-old man with Crohn’s disease revealed active disease in the ileum and sigmoid colon with narrowing at the recto-sigmoid colon. The MRE revealed active inflammation at the ileo-colonic anastomosis and of the sigmoid and descending colon, with no noted fistulas. His physician solicits advice in the forum on next steps for the patient, who was experiencing significant pain daily, despite being on a low residue diet and consistent drug therapy.
Other popular clinical discussions:
• WATS imaging in Barrett’s esophagus (http://ow.ly/PrJ330oHdCN)
Members share their opinions and experiences with Wide-Area Transepithelial Sampling (WATS) in Barrett’s esophagus (BE) after mention of recent data demonstrating its promising potential for surveillance in BE patients, despite not yet being approved by the FDA.
• Positive FIT with negative colonoscopy (http://ow.ly/zSxC30oHcZM)
A physician solicits advice on next steps in managing average-risk patients with a positive FIT and negative colonoscopy screening, and asks colleagues if their actions would change after discovering a patient also had non-bleeding hemorrhoids on exam.
More clinical cases and discussions are at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org/discussions) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses.
In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Perianal fistula found in UC patient (http://ow.ly/S8bJ30okWuO)
A 20-year-old male patient with no previous medical history was seen and treated last year for pancolitis. His physician solicits drug therapy preferences from the GI community, given the age of the patient and a newly discovered perianal fistula.
2. IBD patient with risk of cancer (http://ow.ly/KoGz30oHdjG)
A 62-year-old female patient with a long history of Crohn’s disease developed acute hepatitis. She had a colectomy in 2011 where a one-stage ileo rectal anastomosis was performed instead of a J-pouch. She was in remission under surveillance and mesalamine, until recently. She also has primary sclerosing cholangitis (PSC) and multifocal dysplasia, a combination that raised concern among the GI community about the patient’s risk of cancer.
3. Significant daily pain in Crohn’s patient (http://ow.ly/FHUI30oHdI8)
A recent colonoscopy for a 39-year-old man with Crohn’s disease revealed active disease in the ileum and sigmoid colon with narrowing at the recto-sigmoid colon. The MRE revealed active inflammation at the ileo-colonic anastomosis and of the sigmoid and descending colon, with no noted fistulas. His physician solicits advice in the forum on next steps for the patient, who was experiencing significant pain daily, despite being on a low residue diet and consistent drug therapy.
Other popular clinical discussions:
• WATS imaging in Barrett’s esophagus (http://ow.ly/PrJ330oHdCN)
Members share their opinions and experiences with Wide-Area Transepithelial Sampling (WATS) in Barrett’s esophagus (BE) after mention of recent data demonstrating its promising potential for surveillance in BE patients, despite not yet being approved by the FDA.
• Positive FIT with negative colonoscopy (http://ow.ly/zSxC30oHcZM)
A physician solicits advice on next steps in managing average-risk patients with a positive FIT and negative colonoscopy screening, and asks colleagues if their actions would change after discovering a patient also had non-bleeding hemorrhoids on exam.
More clinical cases and discussions are at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org/discussions) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses.
In case you missed it, here are the most popular clinical discussions shared in the forum recently:
1. Perianal fistula found in UC patient (http://ow.ly/S8bJ30okWuO)
A 20-year-old male patient with no previous medical history was seen and treated last year for pancolitis. His physician solicits drug therapy preferences from the GI community, given the age of the patient and a newly discovered perianal fistula.
2. IBD patient with risk of cancer (http://ow.ly/KoGz30oHdjG)
A 62-year-old female patient with a long history of Crohn’s disease developed acute hepatitis. She had a colectomy in 2011 where a one-stage ileo rectal anastomosis was performed instead of a J-pouch. She was in remission under surveillance and mesalamine, until recently. She also has primary sclerosing cholangitis (PSC) and multifocal dysplasia, a combination that raised concern among the GI community about the patient’s risk of cancer.
3. Significant daily pain in Crohn’s patient (http://ow.ly/FHUI30oHdI8)
A recent colonoscopy for a 39-year-old man with Crohn’s disease revealed active disease in the ileum and sigmoid colon with narrowing at the recto-sigmoid colon. The MRE revealed active inflammation at the ileo-colonic anastomosis and of the sigmoid and descending colon, with no noted fistulas. His physician solicits advice in the forum on next steps for the patient, who was experiencing significant pain daily, despite being on a low residue diet and consistent drug therapy.
Other popular clinical discussions:
• WATS imaging in Barrett’s esophagus (http://ow.ly/PrJ330oHdCN)
Members share their opinions and experiences with Wide-Area Transepithelial Sampling (WATS) in Barrett’s esophagus (BE) after mention of recent data demonstrating its promising potential for surveillance in BE patients, despite not yet being approved by the FDA.
• Positive FIT with negative colonoscopy (http://ow.ly/zSxC30oHcZM)
A physician solicits advice on next steps in managing average-risk patients with a positive FIT and negative colonoscopy screening, and asks colleagues if their actions would change after discovering a patient also had non-bleeding hemorrhoids on exam.
More clinical cases and discussions are at https://community.gastro.org/discussions.
Food the focus of gut health at 2019 Freston Conference
Recognition is increasing among GI practitioners about the influence of nutrition and diet on patient outcomes. From irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac, mast cell activation syndrome, and other maladies, what patients consume plays a role in how well they combat these diseases. Increasingly, clinicians are working with allied health professionals including allergists, nutritionists, and dietitians to forge partnerships to promote sound gut health. In response to this growing trend, the 2019 James W. Freston Conference – Food at the Intersection of Gut Health and Disease, Aug. 9-10, 2019, in Chicago, will examine how nutrition management therapies can combat GI disorders and how diet supports improvement across the care continuum.
Since 2008, Freston has focused on single-issue topics where experts gather to address practitioner challenges and solutions as well as gastroenterological science. Following this year’s Freston, attendees will leave with a deep understanding about:
• How to recognize and differentiate food-induced GI disorders.
• Diets that promote sound gut health care.
• How nutrient-gene interactions may alter gastrointestinal conditions.
• How nutrition can help patients with gastroesophageal reflux disease (GERD), IBS, IBD, FGIDs and mast cell activation syndrome.
• Implementing nutrition management therapies.
Join like-minded practitioners and industry counterparts in Freston’s intimate environment designed to foster learning, networking, and engagement. Registration is open and early bird rates are in effect through June 5. Learn more by visiting freston.gastro.org
Recognition is increasing among GI practitioners about the influence of nutrition and diet on patient outcomes. From irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac, mast cell activation syndrome, and other maladies, what patients consume plays a role in how well they combat these diseases. Increasingly, clinicians are working with allied health professionals including allergists, nutritionists, and dietitians to forge partnerships to promote sound gut health. In response to this growing trend, the 2019 James W. Freston Conference – Food at the Intersection of Gut Health and Disease, Aug. 9-10, 2019, in Chicago, will examine how nutrition management therapies can combat GI disorders and how diet supports improvement across the care continuum.
Since 2008, Freston has focused on single-issue topics where experts gather to address practitioner challenges and solutions as well as gastroenterological science. Following this year’s Freston, attendees will leave with a deep understanding about:
• How to recognize and differentiate food-induced GI disorders.
• Diets that promote sound gut health care.
• How nutrient-gene interactions may alter gastrointestinal conditions.
• How nutrition can help patients with gastroesophageal reflux disease (GERD), IBS, IBD, FGIDs and mast cell activation syndrome.
• Implementing nutrition management therapies.
Join like-minded practitioners and industry counterparts in Freston’s intimate environment designed to foster learning, networking, and engagement. Registration is open and early bird rates are in effect through June 5. Learn more by visiting freston.gastro.org
Recognition is increasing among GI practitioners about the influence of nutrition and diet on patient outcomes. From irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac, mast cell activation syndrome, and other maladies, what patients consume plays a role in how well they combat these diseases. Increasingly, clinicians are working with allied health professionals including allergists, nutritionists, and dietitians to forge partnerships to promote sound gut health. In response to this growing trend, the 2019 James W. Freston Conference – Food at the Intersection of Gut Health and Disease, Aug. 9-10, 2019, in Chicago, will examine how nutrition management therapies can combat GI disorders and how diet supports improvement across the care continuum.
Since 2008, Freston has focused on single-issue topics where experts gather to address practitioner challenges and solutions as well as gastroenterological science. Following this year’s Freston, attendees will leave with a deep understanding about:
• How to recognize and differentiate food-induced GI disorders.
• Diets that promote sound gut health care.
• How nutrient-gene interactions may alter gastrointestinal conditions.
• How nutrition can help patients with gastroesophageal reflux disease (GERD), IBS, IBD, FGIDs and mast cell activation syndrome.
• Implementing nutrition management therapies.
Join like-minded practitioners and industry counterparts in Freston’s intimate environment designed to foster learning, networking, and engagement. Registration is open and early bird rates are in effect through June 5. Learn more by visiting freston.gastro.org
SC-PEG comparable to pegaspargase in young ALL/LL patients
CHICAGO – Calaspargase pegol (SC-PEG) produces similar outcomes as standard pegaspargase in pediatric and young adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), according to a phase 2 trial.
Patients who received SC-PEG every 3 weeks had similar serum asparaginase activity (SAA), toxicities, and survival rates as patients who received standard pegaspargase every 2 weeks.
Lynda M. Vrooman, MD, of Dana-Farber Cancer Institute in Boston, presented these results at the annual meeting of the American Society of Clinical Oncology.
The trial (NCT01574274) enrolled 239 patients, 230 with ALL and 9 with LL. Most patients had B-cell (n = 207) disease. The patients’ median age was 5.2 years (range, 1.0-20.9 years).
“There were no differences in presenting features by randomization,” Dr. Vrooman noted.
The patients were randomized to receive pegaspargase (n = 120) or SC-PEG (n = 119), a pegylated asparaginase formulation with longer half-life. SC-PEG was given at 2,500 IU/m2 every 3 weeks, and pegaspargase was given at 2,500 IU/m2 every 2 weeks.
Either asparaginase product was given as part of a 4-week induction regimen (vincristine, prednisone, doxorubicin, and methotrexate), a 3-week intensification regimen (intrathecal chemotherapy with or without radiotherapy) for central nervous system disease, and a 27-week second consolidation regimen (mercaptopurine, methotrexate, and, in high-risk patients, doxorubicin).
SAA
The researchers observed significantly longer SAA with SC-PEG during induction but not after.
During induction, at 25 days after the first asparaginase dose, 88% of patients on SC-PEG and 17% of those on pegaspargase had SAA of at least 0.10 IU/mL (P less than .001). Post-induction, at week 25, 100% of patients in each group had a nadir SAA of at least 0.10 IU/mL.
“The high nadir serum asparaginase activity levels observed for both preparations suggest dosing strategies could be further optimized,” Dr. Vrooman noted.
Safety
There were no significant differences in adverse events between the SC-PEG and pegaspargase arms during or after induction.
Adverse events during induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (0% and 1%), grade 2 or higher pancreatitis (3% in both), grade 2 or higher thrombosis (3% and 9%), grade 4 hyperbilirubinemia (3% and 1%), grade 3 or higher bacterial infection (12% and 9%), and grade 3 or higher fungal infection (4% and 5%).
Adverse events after induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (17% and 14%), grade 2 or higher pancreatitis (15% in both), grade 2 or higher thrombosis (18% and 13%), grade 4 hyperbilirubinemia (4% and 3%), grade 3 or higher bacterial infection (12% and 15%), grade 3 or higher fungal infection (2% and 1%), grade 2 or higher bone fracture (3% and 8%), and grade 2 or higher osteonecrosis (3% and 4%).
Response and survival
The complete response rate was 95% (109/115) in the SC-PEG arm and 99% (114/115) in the pegaspargase arm. Rates of induction failure were 3% (n = 4) and 1% (n = 1), respectively, and rates of relapse were 3% (n = 5) and 8% (n = 10), respectively.
There were two induction deaths and two remission deaths in the SC-PEG arm but no induction or remission deaths in the pegaspargase arm.
The median follow-up was 4 years. The 4-year event-free survival rate was 87.7% with SC-PEG and 90.2% with pegaspargase (P = .78). The 4-year overall survival rate was 94.8% and 95.6%, respectively (P = .74).
In closing, Dr. Vrooman said these data suggest SC-PEG provides similar results as standard pegaspargase. She noted that these data informed the U.S. approval of SC-PEG for pediatric and young adult ALL.
This trial was sponsored by the Dana-Farber Cancer Institute in collaboration with Shire and the National Cancer Institute. Dr. Vrooman said she had no relationships to disclose.
SOURCE: Vrooman LM et al. ASCO 2019. Abstract 10006.
CHICAGO – Calaspargase pegol (SC-PEG) produces similar outcomes as standard pegaspargase in pediatric and young adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), according to a phase 2 trial.
Patients who received SC-PEG every 3 weeks had similar serum asparaginase activity (SAA), toxicities, and survival rates as patients who received standard pegaspargase every 2 weeks.
Lynda M. Vrooman, MD, of Dana-Farber Cancer Institute in Boston, presented these results at the annual meeting of the American Society of Clinical Oncology.
The trial (NCT01574274) enrolled 239 patients, 230 with ALL and 9 with LL. Most patients had B-cell (n = 207) disease. The patients’ median age was 5.2 years (range, 1.0-20.9 years).
“There were no differences in presenting features by randomization,” Dr. Vrooman noted.
The patients were randomized to receive pegaspargase (n = 120) or SC-PEG (n = 119), a pegylated asparaginase formulation with longer half-life. SC-PEG was given at 2,500 IU/m2 every 3 weeks, and pegaspargase was given at 2,500 IU/m2 every 2 weeks.
Either asparaginase product was given as part of a 4-week induction regimen (vincristine, prednisone, doxorubicin, and methotrexate), a 3-week intensification regimen (intrathecal chemotherapy with or without radiotherapy) for central nervous system disease, and a 27-week second consolidation regimen (mercaptopurine, methotrexate, and, in high-risk patients, doxorubicin).
SAA
The researchers observed significantly longer SAA with SC-PEG during induction but not after.
During induction, at 25 days after the first asparaginase dose, 88% of patients on SC-PEG and 17% of those on pegaspargase had SAA of at least 0.10 IU/mL (P less than .001). Post-induction, at week 25, 100% of patients in each group had a nadir SAA of at least 0.10 IU/mL.
“The high nadir serum asparaginase activity levels observed for both preparations suggest dosing strategies could be further optimized,” Dr. Vrooman noted.
Safety
There were no significant differences in adverse events between the SC-PEG and pegaspargase arms during or after induction.
Adverse events during induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (0% and 1%), grade 2 or higher pancreatitis (3% in both), grade 2 or higher thrombosis (3% and 9%), grade 4 hyperbilirubinemia (3% and 1%), grade 3 or higher bacterial infection (12% and 9%), and grade 3 or higher fungal infection (4% and 5%).
Adverse events after induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (17% and 14%), grade 2 or higher pancreatitis (15% in both), grade 2 or higher thrombosis (18% and 13%), grade 4 hyperbilirubinemia (4% and 3%), grade 3 or higher bacterial infection (12% and 15%), grade 3 or higher fungal infection (2% and 1%), grade 2 or higher bone fracture (3% and 8%), and grade 2 or higher osteonecrosis (3% and 4%).
Response and survival
The complete response rate was 95% (109/115) in the SC-PEG arm and 99% (114/115) in the pegaspargase arm. Rates of induction failure were 3% (n = 4) and 1% (n = 1), respectively, and rates of relapse were 3% (n = 5) and 8% (n = 10), respectively.
There were two induction deaths and two remission deaths in the SC-PEG arm but no induction or remission deaths in the pegaspargase arm.
The median follow-up was 4 years. The 4-year event-free survival rate was 87.7% with SC-PEG and 90.2% with pegaspargase (P = .78). The 4-year overall survival rate was 94.8% and 95.6%, respectively (P = .74).
In closing, Dr. Vrooman said these data suggest SC-PEG provides similar results as standard pegaspargase. She noted that these data informed the U.S. approval of SC-PEG for pediatric and young adult ALL.
This trial was sponsored by the Dana-Farber Cancer Institute in collaboration with Shire and the National Cancer Institute. Dr. Vrooman said she had no relationships to disclose.
SOURCE: Vrooman LM et al. ASCO 2019. Abstract 10006.
CHICAGO – Calaspargase pegol (SC-PEG) produces similar outcomes as standard pegaspargase in pediatric and young adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL), according to a phase 2 trial.
Patients who received SC-PEG every 3 weeks had similar serum asparaginase activity (SAA), toxicities, and survival rates as patients who received standard pegaspargase every 2 weeks.
Lynda M. Vrooman, MD, of Dana-Farber Cancer Institute in Boston, presented these results at the annual meeting of the American Society of Clinical Oncology.
The trial (NCT01574274) enrolled 239 patients, 230 with ALL and 9 with LL. Most patients had B-cell (n = 207) disease. The patients’ median age was 5.2 years (range, 1.0-20.9 years).
“There were no differences in presenting features by randomization,” Dr. Vrooman noted.
The patients were randomized to receive pegaspargase (n = 120) or SC-PEG (n = 119), a pegylated asparaginase formulation with longer half-life. SC-PEG was given at 2,500 IU/m2 every 3 weeks, and pegaspargase was given at 2,500 IU/m2 every 2 weeks.
Either asparaginase product was given as part of a 4-week induction regimen (vincristine, prednisone, doxorubicin, and methotrexate), a 3-week intensification regimen (intrathecal chemotherapy with or without radiotherapy) for central nervous system disease, and a 27-week second consolidation regimen (mercaptopurine, methotrexate, and, in high-risk patients, doxorubicin).
SAA
The researchers observed significantly longer SAA with SC-PEG during induction but not after.
During induction, at 25 days after the first asparaginase dose, 88% of patients on SC-PEG and 17% of those on pegaspargase had SAA of at least 0.10 IU/mL (P less than .001). Post-induction, at week 25, 100% of patients in each group had a nadir SAA of at least 0.10 IU/mL.
“The high nadir serum asparaginase activity levels observed for both preparations suggest dosing strategies could be further optimized,” Dr. Vrooman noted.
Safety
There were no significant differences in adverse events between the SC-PEG and pegaspargase arms during or after induction.
Adverse events during induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (0% and 1%), grade 2 or higher pancreatitis (3% in both), grade 2 or higher thrombosis (3% and 9%), grade 4 hyperbilirubinemia (3% and 1%), grade 3 or higher bacterial infection (12% and 9%), and grade 3 or higher fungal infection (4% and 5%).
Adverse events after induction (in the SC-PEG and pegaspargase arms, respectively) included grade 2 or higher asparaginase allergy (17% and 14%), grade 2 or higher pancreatitis (15% in both), grade 2 or higher thrombosis (18% and 13%), grade 4 hyperbilirubinemia (4% and 3%), grade 3 or higher bacterial infection (12% and 15%), grade 3 or higher fungal infection (2% and 1%), grade 2 or higher bone fracture (3% and 8%), and grade 2 or higher osteonecrosis (3% and 4%).
Response and survival
The complete response rate was 95% (109/115) in the SC-PEG arm and 99% (114/115) in the pegaspargase arm. Rates of induction failure were 3% (n = 4) and 1% (n = 1), respectively, and rates of relapse were 3% (n = 5) and 8% (n = 10), respectively.
There were two induction deaths and two remission deaths in the SC-PEG arm but no induction or remission deaths in the pegaspargase arm.
The median follow-up was 4 years. The 4-year event-free survival rate was 87.7% with SC-PEG and 90.2% with pegaspargase (P = .78). The 4-year overall survival rate was 94.8% and 95.6%, respectively (P = .74).
In closing, Dr. Vrooman said these data suggest SC-PEG provides similar results as standard pegaspargase. She noted that these data informed the U.S. approval of SC-PEG for pediatric and young adult ALL.
This trial was sponsored by the Dana-Farber Cancer Institute in collaboration with Shire and the National Cancer Institute. Dr. Vrooman said she had no relationships to disclose.
SOURCE: Vrooman LM et al. ASCO 2019. Abstract 10006.
REPORTING FROM ASCO 2019
Scope-associated infection still a concern in the US
On April 12, FDA issued a safety communication releasing new information on the duodenoscope contamination rate from postmarket surveillance studies and medical device reports. While the outlook has improved significantly since this issue first arose in 2015, we are not yet at our goal of zero device-associated infections.
AGA encourages all members to stay vigilant when it comes to duodenoscope reprocessing and strictly adhere to the manufacturer’s reprocessing and maintenance instructions.
In the safety communication, FDA reports:
• In the past 6 months, three people died and 45 people developed infections from contaminated endoscopes.
• Results from sampling studies show up to 5.4% of all properly collected samples tested positive for “high concern” organisms. “High concern” bacteria are more often associated with disease, such as E. coli or Staphylococcus aureus.
• Additionally, up to 3.6% of properly collected samples tested positive for low to moderate concern organisms; while these organisms don’t usually lead to dangerous infections, they are indicative of a reprocessing failure.
Jeff Shuren, MD, director of the Center for Devices and Radiological Health at FDA, also issued a communication on continued efforts to assess duodenoscope contamination risk. Dr. Shuren puts this new data into perspective:
“While the current contamination rates we’re seeing in the postmarket studies show the need for improvement, I want to emphasize that an individual patient’s risk of acquiring infection from an inadequately reprocessed medical device remains relatively low given the large number of such devices in use.”
The AGA Center for GI Innovation and Technology (CGIT) continuously monitors this issue and engages with industry and FDA on efforts that will help us reach our goal of zero device-transmitted infections to our patients.
“We continually meet with industry partners, just as recently as last week at the AGA Tech Summit, to understand how they are innovating to reduce the risk of potential infection. We are also in close communication with FDA and other key stakeholders. We all have a role in preventing device-transmitted infections, and we don’t take our role lightly,” added V. Raman Muthusamy, MD, AGAF, FACG, FASGE, chair of the AGA CGIT.
On April 12, FDA issued a safety communication releasing new information on the duodenoscope contamination rate from postmarket surveillance studies and medical device reports. While the outlook has improved significantly since this issue first arose in 2015, we are not yet at our goal of zero device-associated infections.
AGA encourages all members to stay vigilant when it comes to duodenoscope reprocessing and strictly adhere to the manufacturer’s reprocessing and maintenance instructions.
In the safety communication, FDA reports:
• In the past 6 months, three people died and 45 people developed infections from contaminated endoscopes.
• Results from sampling studies show up to 5.4% of all properly collected samples tested positive for “high concern” organisms. “High concern” bacteria are more often associated with disease, such as E. coli or Staphylococcus aureus.
• Additionally, up to 3.6% of properly collected samples tested positive for low to moderate concern organisms; while these organisms don’t usually lead to dangerous infections, they are indicative of a reprocessing failure.
Jeff Shuren, MD, director of the Center for Devices and Radiological Health at FDA, also issued a communication on continued efforts to assess duodenoscope contamination risk. Dr. Shuren puts this new data into perspective:
“While the current contamination rates we’re seeing in the postmarket studies show the need for improvement, I want to emphasize that an individual patient’s risk of acquiring infection from an inadequately reprocessed medical device remains relatively low given the large number of such devices in use.”
The AGA Center for GI Innovation and Technology (CGIT) continuously monitors this issue and engages with industry and FDA on efforts that will help us reach our goal of zero device-transmitted infections to our patients.
“We continually meet with industry partners, just as recently as last week at the AGA Tech Summit, to understand how they are innovating to reduce the risk of potential infection. We are also in close communication with FDA and other key stakeholders. We all have a role in preventing device-transmitted infections, and we don’t take our role lightly,” added V. Raman Muthusamy, MD, AGAF, FACG, FASGE, chair of the AGA CGIT.
On April 12, FDA issued a safety communication releasing new information on the duodenoscope contamination rate from postmarket surveillance studies and medical device reports. While the outlook has improved significantly since this issue first arose in 2015, we are not yet at our goal of zero device-associated infections.
AGA encourages all members to stay vigilant when it comes to duodenoscope reprocessing and strictly adhere to the manufacturer’s reprocessing and maintenance instructions.
In the safety communication, FDA reports:
• In the past 6 months, three people died and 45 people developed infections from contaminated endoscopes.
• Results from sampling studies show up to 5.4% of all properly collected samples tested positive for “high concern” organisms. “High concern” bacteria are more often associated with disease, such as E. coli or Staphylococcus aureus.
• Additionally, up to 3.6% of properly collected samples tested positive for low to moderate concern organisms; while these organisms don’t usually lead to dangerous infections, they are indicative of a reprocessing failure.
Jeff Shuren, MD, director of the Center for Devices and Radiological Health at FDA, also issued a communication on continued efforts to assess duodenoscope contamination risk. Dr. Shuren puts this new data into perspective:
“While the current contamination rates we’re seeing in the postmarket studies show the need for improvement, I want to emphasize that an individual patient’s risk of acquiring infection from an inadequately reprocessed medical device remains relatively low given the large number of such devices in use.”
The AGA Center for GI Innovation and Technology (CGIT) continuously monitors this issue and engages with industry and FDA on efforts that will help us reach our goal of zero device-transmitted infections to our patients.
“We continually meet with industry partners, just as recently as last week at the AGA Tech Summit, to understand how they are innovating to reduce the risk of potential infection. We are also in close communication with FDA and other key stakeholders. We all have a role in preventing device-transmitted infections, and we don’t take our role lightly,” added V. Raman Muthusamy, MD, AGAF, FACG, FASGE, chair of the AGA CGIT.
A doctor in the House: Rep. Raul Ruiz is fighting for GIs and our patients
Rep. Ruiz was a virtually unknown candidate and defeated then incumbent Mary Bono, R-CA, for the seat that represents Coachella Valley and Palm Springs. Rep. Ruiz is the son of migrant farmers from Mexico who went on to medical school and became the first Latino to receive three graduate degrees from Harvard — a medical degree, a masters of public policy, and a masters of public health. Rep. Ruiz is an emergency physician by training and AGA got to know him early in his congressional career and provided support for his initiatives that aligned with our policy priorities and support through AGA PAC.
When Rep. Ruiz was elected to Congress, the Democrats were in the minority in the House and as a freshman member in the minority, did not yield a lot of power and influence. However, AGA continued to work with Rep. Ruiz in garnering his support for repealing the Independent Payment Advisory Board (IPAB) that was created under the Affordable Care Act (ACA) — it was charged with making budgetary decisions for the Medicare program that would have disproportionately impacted physicians. Rep. Ruiz was willing to work with Republicans to support legislation to repeal IPAB; Congress eventually repealed it in the last Congress.
AGA also worked with Rep. Ruiz in support of increasing access to colorectal cancer screening especially for underrepresented minorities and he has been a strong supporter of the Removing Barriers to Colorectal Cancer Screening Act that would fix the current Medicare screening colonoscopy coinsurance problem that disproportionately impacts poorer Medicare beneficiaries who lack supplemental coverage.
Recently, AGA has been working closely with Rep. Ruiz as he champions an issue that impacts GI patients with inflammatory bowel disease and their ability to access the treatment that their doctor recommends. Rep. Ruiz has introduced H.R. 2279, the Safe Step Act, legislation that would provide a clear, transparent, and easily accessible appeals process for physicians and their patients when subject to step therapy protocols. Step therapy, also known as “fail first,” requires patients to try and fail one or more medications before the insurer will provide coverage for the therapy that their doctor thinks is the best to manage their condition. The Safe Step Act would not eliminate step therapy but would provide some common sense guardrails for patients and reasonable exceptions for patients who would be harmed if subjected to such a policy.
Because of AGA PAC’s and other physician organizations’ PAC support for Rep. Ruiz, he was able to secure a seat on the highly coveted Energy and Commerce Committee and its Health Subcommittee. The Committee has jurisdiction over all public health programs such as NIH, CDC, FDA, and Medicare Part B which is all physician services. Given Rep. Ruiz’s background and the committee position he holds, he is well-suited to continue to help champion AGA’s policy priorities and those of all organized medicine.
Over the years, Rep. Ruiz has spoken to AGA members at our annual Advocacy Day on the importance of physicians being involved politically and also in advocacy. He has also met with AGA Government Affairs Committee member Gaurav Singhvi, MD, in the district on issues important to the gastroenterology community and our patients.
AGA looks forward to working with Rep. Ruiz to continue to ensure that patients have access to specialty care, that the administrative burdens that physicians face like prior authorization are reduced, we continue to invest in research, and that we continue to train the next generation of GIs.
Rep. Ruiz was a virtually unknown candidate and defeated then incumbent Mary Bono, R-CA, for the seat that represents Coachella Valley and Palm Springs. Rep. Ruiz is the son of migrant farmers from Mexico who went on to medical school and became the first Latino to receive three graduate degrees from Harvard — a medical degree, a masters of public policy, and a masters of public health. Rep. Ruiz is an emergency physician by training and AGA got to know him early in his congressional career and provided support for his initiatives that aligned with our policy priorities and support through AGA PAC.
When Rep. Ruiz was elected to Congress, the Democrats were in the minority in the House and as a freshman member in the minority, did not yield a lot of power and influence. However, AGA continued to work with Rep. Ruiz in garnering his support for repealing the Independent Payment Advisory Board (IPAB) that was created under the Affordable Care Act (ACA) — it was charged with making budgetary decisions for the Medicare program that would have disproportionately impacted physicians. Rep. Ruiz was willing to work with Republicans to support legislation to repeal IPAB; Congress eventually repealed it in the last Congress.
AGA also worked with Rep. Ruiz in support of increasing access to colorectal cancer screening especially for underrepresented minorities and he has been a strong supporter of the Removing Barriers to Colorectal Cancer Screening Act that would fix the current Medicare screening colonoscopy coinsurance problem that disproportionately impacts poorer Medicare beneficiaries who lack supplemental coverage.
Recently, AGA has been working closely with Rep. Ruiz as he champions an issue that impacts GI patients with inflammatory bowel disease and their ability to access the treatment that their doctor recommends. Rep. Ruiz has introduced H.R. 2279, the Safe Step Act, legislation that would provide a clear, transparent, and easily accessible appeals process for physicians and their patients when subject to step therapy protocols. Step therapy, also known as “fail first,” requires patients to try and fail one or more medications before the insurer will provide coverage for the therapy that their doctor thinks is the best to manage their condition. The Safe Step Act would not eliminate step therapy but would provide some common sense guardrails for patients and reasonable exceptions for patients who would be harmed if subjected to such a policy.
Because of AGA PAC’s and other physician organizations’ PAC support for Rep. Ruiz, he was able to secure a seat on the highly coveted Energy and Commerce Committee and its Health Subcommittee. The Committee has jurisdiction over all public health programs such as NIH, CDC, FDA, and Medicare Part B which is all physician services. Given Rep. Ruiz’s background and the committee position he holds, he is well-suited to continue to help champion AGA’s policy priorities and those of all organized medicine.
Over the years, Rep. Ruiz has spoken to AGA members at our annual Advocacy Day on the importance of physicians being involved politically and also in advocacy. He has also met with AGA Government Affairs Committee member Gaurav Singhvi, MD, in the district on issues important to the gastroenterology community and our patients.
AGA looks forward to working with Rep. Ruiz to continue to ensure that patients have access to specialty care, that the administrative burdens that physicians face like prior authorization are reduced, we continue to invest in research, and that we continue to train the next generation of GIs.
Rep. Ruiz was a virtually unknown candidate and defeated then incumbent Mary Bono, R-CA, for the seat that represents Coachella Valley and Palm Springs. Rep. Ruiz is the son of migrant farmers from Mexico who went on to medical school and became the first Latino to receive three graduate degrees from Harvard — a medical degree, a masters of public policy, and a masters of public health. Rep. Ruiz is an emergency physician by training and AGA got to know him early in his congressional career and provided support for his initiatives that aligned with our policy priorities and support through AGA PAC.
When Rep. Ruiz was elected to Congress, the Democrats were in the minority in the House and as a freshman member in the minority, did not yield a lot of power and influence. However, AGA continued to work with Rep. Ruiz in garnering his support for repealing the Independent Payment Advisory Board (IPAB) that was created under the Affordable Care Act (ACA) — it was charged with making budgetary decisions for the Medicare program that would have disproportionately impacted physicians. Rep. Ruiz was willing to work with Republicans to support legislation to repeal IPAB; Congress eventually repealed it in the last Congress.
AGA also worked with Rep. Ruiz in support of increasing access to colorectal cancer screening especially for underrepresented minorities and he has been a strong supporter of the Removing Barriers to Colorectal Cancer Screening Act that would fix the current Medicare screening colonoscopy coinsurance problem that disproportionately impacts poorer Medicare beneficiaries who lack supplemental coverage.
Recently, AGA has been working closely with Rep. Ruiz as he champions an issue that impacts GI patients with inflammatory bowel disease and their ability to access the treatment that their doctor recommends. Rep. Ruiz has introduced H.R. 2279, the Safe Step Act, legislation that would provide a clear, transparent, and easily accessible appeals process for physicians and their patients when subject to step therapy protocols. Step therapy, also known as “fail first,” requires patients to try and fail one or more medications before the insurer will provide coverage for the therapy that their doctor thinks is the best to manage their condition. The Safe Step Act would not eliminate step therapy but would provide some common sense guardrails for patients and reasonable exceptions for patients who would be harmed if subjected to such a policy.
Because of AGA PAC’s and other physician organizations’ PAC support for Rep. Ruiz, he was able to secure a seat on the highly coveted Energy and Commerce Committee and its Health Subcommittee. The Committee has jurisdiction over all public health programs such as NIH, CDC, FDA, and Medicare Part B which is all physician services. Given Rep. Ruiz’s background and the committee position he holds, he is well-suited to continue to help champion AGA’s policy priorities and those of all organized medicine.
Over the years, Rep. Ruiz has spoken to AGA members at our annual Advocacy Day on the importance of physicians being involved politically and also in advocacy. He has also met with AGA Government Affairs Committee member Gaurav Singhvi, MD, in the district on issues important to the gastroenterology community and our patients.
AGA looks forward to working with Rep. Ruiz to continue to ensure that patients have access to specialty care, that the administrative burdens that physicians face like prior authorization are reduced, we continue to invest in research, and that we continue to train the next generation of GIs.
Low intensity bridging may be best path to CAR T in adult ALL
CHICAGO – A low intensity chemotherapy regimen may be the best approach to bridge patients waiting for chimeric antigen receptor (CAR) T-cell therapy, according to a retrospective analysis of adults with acute lymphoblastic leukemia (ALL).
Investigators found that high intensity bridging regimens provided no clear outcome benefit, but did produce a greater number of infections.
But the decision on the type of regimen is very much dependent on the individual patient, Karlo Perica, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the annual meeting of the American Society of Clinical Oncology.
Dr. Perica and his colleagues at Memorial Sloan Kettering examined the effectiveness and toxicity of bridging therapies provided to relapsed or refractory ALL patients waiting to receive CD19 CAR T-cell therapy as part of a phase 1 trial (N Engl J Med. 2018 Feb 1;378[5]:449-59).
Bridging therapy was defined as any therapy given from leukapheresis to cell infusion.
The low-intensity regimens included POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone, or combinations), liposomal vincristine, mini-hyper CVD (reduced cyclophosphamide, dexamethasone, methotrexate, Ara-C), blinatumomab, inotuzumab, oral tyrosine kinase inhibitor-based regimens, or hydroxyurea.
The high-intensity regimens included hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose cytarabine, attenuated FLAG/FLAG-IDA (reduced fludarabine, cytarabine, G-CSF plus or minus idarubicin), and pediatric-type induction.
Of the 53 patients who were ultimately infused with CAR T cells, 19 received some type of high intensity regimen, 29 received low intensity regimens, and 5 received no bridging treatment. The group overall was heavily pretreated. Nearly a third of the low intensity and no bridging patients and 42% of the high intensity patients had previously undergone transplant. More than 40% of the low intensity and no bridging patients and about a quarter of the high intensity bridging group had four or more prior lines of therapy.
The use of high intensity bridging therapy was not associated with improved overall response or relapse-free survival to CAR T-cell therapy, the investigators reported. In a subgroup with 23 high disease burden patients with greater than 20% blasts, there was no difference in MRD-negative complete response by intensity (75% versus 60%, Fisher’s P = .65).
High intensity bridging was also not associated with successful CAR T-cell infusion, versus low intensity regimens (63% versus 79%, P greater than .05) or a combined endpoint of CAR T-cell infusion plus transplant or alternative treatment (80% versus 86%, P greater than .05).
In terms of toxicity, the high intensity bridging regimens were associated with a higher rate of grade 3 or 4 infections – 15 versus 11 infections (Fisher’s P = .002). But there was no association with post-infusion grade 3 or 4 cytokine release syndrome or neurotoxicity.
Dr. Perica said the results reflect that the real goal of bridging is not to reduce disease burden but instead to successfully bring patients to the next phase of their treatment. “The goal of the bridging therapy is to get the patient to the CAR infusion,” he said.
Due to the retrospective nature of the study, Dr. Perica said he can’t recommend any single bridging regimen and he emphasized that the decisions are patient-specific.
The original study was funded by several foundations and Juno Therapeutics. Dr. Perica reported royalties from technology licensed to Neximmune.
SOURCE: Perica K et al. ASCO 2019, Abstract 2520.
CHICAGO – A low intensity chemotherapy regimen may be the best approach to bridge patients waiting for chimeric antigen receptor (CAR) T-cell therapy, according to a retrospective analysis of adults with acute lymphoblastic leukemia (ALL).
Investigators found that high intensity bridging regimens provided no clear outcome benefit, but did produce a greater number of infections.
But the decision on the type of regimen is very much dependent on the individual patient, Karlo Perica, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the annual meeting of the American Society of Clinical Oncology.
Dr. Perica and his colleagues at Memorial Sloan Kettering examined the effectiveness and toxicity of bridging therapies provided to relapsed or refractory ALL patients waiting to receive CD19 CAR T-cell therapy as part of a phase 1 trial (N Engl J Med. 2018 Feb 1;378[5]:449-59).
Bridging therapy was defined as any therapy given from leukapheresis to cell infusion.
The low-intensity regimens included POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone, or combinations), liposomal vincristine, mini-hyper CVD (reduced cyclophosphamide, dexamethasone, methotrexate, Ara-C), blinatumomab, inotuzumab, oral tyrosine kinase inhibitor-based regimens, or hydroxyurea.
The high-intensity regimens included hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose cytarabine, attenuated FLAG/FLAG-IDA (reduced fludarabine, cytarabine, G-CSF plus or minus idarubicin), and pediatric-type induction.
Of the 53 patients who were ultimately infused with CAR T cells, 19 received some type of high intensity regimen, 29 received low intensity regimens, and 5 received no bridging treatment. The group overall was heavily pretreated. Nearly a third of the low intensity and no bridging patients and 42% of the high intensity patients had previously undergone transplant. More than 40% of the low intensity and no bridging patients and about a quarter of the high intensity bridging group had four or more prior lines of therapy.
The use of high intensity bridging therapy was not associated with improved overall response or relapse-free survival to CAR T-cell therapy, the investigators reported. In a subgroup with 23 high disease burden patients with greater than 20% blasts, there was no difference in MRD-negative complete response by intensity (75% versus 60%, Fisher’s P = .65).
High intensity bridging was also not associated with successful CAR T-cell infusion, versus low intensity regimens (63% versus 79%, P greater than .05) or a combined endpoint of CAR T-cell infusion plus transplant or alternative treatment (80% versus 86%, P greater than .05).
In terms of toxicity, the high intensity bridging regimens were associated with a higher rate of grade 3 or 4 infections – 15 versus 11 infections (Fisher’s P = .002). But there was no association with post-infusion grade 3 or 4 cytokine release syndrome or neurotoxicity.
Dr. Perica said the results reflect that the real goal of bridging is not to reduce disease burden but instead to successfully bring patients to the next phase of their treatment. “The goal of the bridging therapy is to get the patient to the CAR infusion,” he said.
Due to the retrospective nature of the study, Dr. Perica said he can’t recommend any single bridging regimen and he emphasized that the decisions are patient-specific.
The original study was funded by several foundations and Juno Therapeutics. Dr. Perica reported royalties from technology licensed to Neximmune.
SOURCE: Perica K et al. ASCO 2019, Abstract 2520.
CHICAGO – A low intensity chemotherapy regimen may be the best approach to bridge patients waiting for chimeric antigen receptor (CAR) T-cell therapy, according to a retrospective analysis of adults with acute lymphoblastic leukemia (ALL).
Investigators found that high intensity bridging regimens provided no clear outcome benefit, but did produce a greater number of infections.
But the decision on the type of regimen is very much dependent on the individual patient, Karlo Perica, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the annual meeting of the American Society of Clinical Oncology.
Dr. Perica and his colleagues at Memorial Sloan Kettering examined the effectiveness and toxicity of bridging therapies provided to relapsed or refractory ALL patients waiting to receive CD19 CAR T-cell therapy as part of a phase 1 trial (N Engl J Med. 2018 Feb 1;378[5]:449-59).
Bridging therapy was defined as any therapy given from leukapheresis to cell infusion.
The low-intensity regimens included POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone, or combinations), liposomal vincristine, mini-hyper CVD (reduced cyclophosphamide, dexamethasone, methotrexate, Ara-C), blinatumomab, inotuzumab, oral tyrosine kinase inhibitor-based regimens, or hydroxyurea.
The high-intensity regimens included hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), high-dose cytarabine, attenuated FLAG/FLAG-IDA (reduced fludarabine, cytarabine, G-CSF plus or minus idarubicin), and pediatric-type induction.
Of the 53 patients who were ultimately infused with CAR T cells, 19 received some type of high intensity regimen, 29 received low intensity regimens, and 5 received no bridging treatment. The group overall was heavily pretreated. Nearly a third of the low intensity and no bridging patients and 42% of the high intensity patients had previously undergone transplant. More than 40% of the low intensity and no bridging patients and about a quarter of the high intensity bridging group had four or more prior lines of therapy.
The use of high intensity bridging therapy was not associated with improved overall response or relapse-free survival to CAR T-cell therapy, the investigators reported. In a subgroup with 23 high disease burden patients with greater than 20% blasts, there was no difference in MRD-negative complete response by intensity (75% versus 60%, Fisher’s P = .65).
High intensity bridging was also not associated with successful CAR T-cell infusion, versus low intensity regimens (63% versus 79%, P greater than .05) or a combined endpoint of CAR T-cell infusion plus transplant or alternative treatment (80% versus 86%, P greater than .05).
In terms of toxicity, the high intensity bridging regimens were associated with a higher rate of grade 3 or 4 infections – 15 versus 11 infections (Fisher’s P = .002). But there was no association with post-infusion grade 3 or 4 cytokine release syndrome or neurotoxicity.
Dr. Perica said the results reflect that the real goal of bridging is not to reduce disease burden but instead to successfully bring patients to the next phase of their treatment. “The goal of the bridging therapy is to get the patient to the CAR infusion,” he said.
Due to the retrospective nature of the study, Dr. Perica said he can’t recommend any single bridging regimen and he emphasized that the decisions are patient-specific.
The original study was funded by several foundations and Juno Therapeutics. Dr. Perica reported royalties from technology licensed to Neximmune.
SOURCE: Perica K et al. ASCO 2019, Abstract 2520.
FROM ASCO 2019
Ribociclib plus endocrine therapy boosts survival of HR+/HER2- breast cancer
CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.
A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.
The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.
In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.
The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.
CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.
A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.
The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.
In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.
The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.
CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.
A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.
The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.
In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.
The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.
REPORTING FROM ASCO 2019
Impetigo: Addressing Treatment Challenges and Burden of Disease
Over the past few decades there has been a shift in the bacteriology and resistance patterns associated with impetigo, making it difficult to identify the best treatment choice for this common bacterial skin infection. In this supplement to Dermatology News, Adelaide A. Hebert, MD and Linda F. Stein Gold, MD, review the current impetigo treatment landscape and the growing concern over methicillin-resistant S. aureus (MRSA).
Over the past few decades there has been a shift in the bacteriology and resistance patterns associated with impetigo, making it difficult to identify the best treatment choice for this common bacterial skin infection. In this supplement to Dermatology News, Adelaide A. Hebert, MD and Linda F. Stein Gold, MD, review the current impetigo treatment landscape and the growing concern over methicillin-resistant S. aureus (MRSA).
Over the past few decades there has been a shift in the bacteriology and resistance patterns associated with impetigo, making it difficult to identify the best treatment choice for this common bacterial skin infection. In this supplement to Dermatology News, Adelaide A. Hebert, MD and Linda F. Stein Gold, MD, review the current impetigo treatment landscape and the growing concern over methicillin-resistant S. aureus (MRSA).
Pembro with or without chemo superior to EXTREME for advanced HNSCC
CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
CHICAGO – Pembrolizumab with and without chemotherapy proved superior for overall survival compared with the EXTREME regimen when used first line in certain subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to “practice-changing” final results from the randomized phase 3 KEYNOTE-048 study.
Compared with 300 patients randomized to receive the EXTREME regimen (a certuximab loading dose followed by carboplatin or cisplatin and 5-fluorouracil), 281 who received pembrolizumab plus chemotherapy (P+C) had superior overall survival (OS) with comparable safety–including both those with programmed death-Ligand 1 (PD-L1) combined positive score (CPS) of 20 or greater (median 14.7 vs 11.0 months; hazard ratio, 0.60) and with CPS of 1 or greater (median, 13.6 vs. 10.4 months; HR, 0.65), Danny Rischin, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The differences were highly statistically significant, said Dr. Rischin, a professor and director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Centre, Melbourne, Australia.
“And this benefit in overall survival in CPS greater than or equal to 20 and greater than or equal to 1 appeared to be present across all the subgroups that we looked at,” he added.
The response rates did not differ between P+C and EXTREME groups, but the median duration of response was significantly greater with P+C vs. EXTREME in both the CPS of 20 or greater and 1 or greater (7.1 vs. 4.2 months and 6.7 vs. 4.3 months, respectively).
Additionally, the final results of the study showed an OS benefit with P+C vs. EXTREME in the total population (13.0 vs. 10.7 months; HR, 0.72), Dr. Rischin said.
The difference between the groups with respect to progression-free survival (PFS), however, was not statistically significant and did not reach the superiority threshold, he noted.
In the 301 patients who received pembrolizumab alone, OS was superior in the CPS 20 or greater and 1 or greater populations (median, 14.8 vs. 10.7 months; HR, 0.58 and 12.4 vs. 10.3 months; HR, 0.74, respectively), compared with EXTREME, but was noninferior in the total population (median 11.5 vs. 10.7 months; HR, 0.83), and safety was favorable .
Again, PFS did not differ between the groups (median, 2.3 vs. 5.2 months; HR, 1.34), and while the overall response rates did not differ significantly, the median duration of response was substantially longer with pembrolizumab at 22.6 vs. 4.5 months with EXTREME, he said.
Study participants had locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting. Those in he P+C arm received pembrolizumab at 200 mg plus 6 cycles of cisplatin at 100 mg/m2 or carboplatin AUC 5, and 5-fluorouracil at a dose of 1000 mg/m2/day for 4 days every 3 weeks; those in the pembrolizumab alone arm received 200 mg every 3 weeks for up to 35 cycles, and those in the EXTREME arm received certuximab at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly with carboplatin AUC 5 or cisplatin at 100 mg/m2, and 5-FU at 1000 mg/m2/day for 4 days for 6 cycles.
“The data from KEYNOTE-048 support pembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy as new standard of care monotherapies for recurrent/metastatic head and neck squamous cell carcinoma,” he concluded.
Discussant Vanita Noronha, MD, a professor in the Department of Medical Oncology at Tata Memorial Hospital in Mumbai, India, said that while the findings are practice changing, they also raise a number of questions, such as which patients should get pembrolizumab and which should get P+C, why there is a differential effect of pembrolizumab based on PD-L1 by CPS–and what about those with CPS of 0 or 1-20, and why the response rates and PFS rates were not improved in the pembrolizumab groups.
Other important questions include whether there are predictive biomarkers for response, and whether sequential therapy would be of benefit, she added.
While these and other questions remain to be addressed, the KEYNOTE-048 findings have implications for practice going forward; based on the current data, her approach to treating patients with R/M HNSCC not amenable to radical therapy is to treat with pembrolizumab alone in those with disease-free interval of 6 months or less, she said.
For those with disease-free interval greater than 6 months and good performance status who have controlled comorbidities, are platinum eligible, and for whom the treatment is reimbursable/affordable, treatment depends on symptom severity; she would treat those with mild/moderate symptoms and CPS of 20 or greater with pembrolizumab alone, those with CPS of 1 or greater with P+C or pembrolizumab alone, and those with CPS of 0 or unknown CPS with EXTREME or a similar regimen or with P+C, and she would treat those with severe symptoms with P+C.
“If the patient were a bit borderline, had multiple comorbidities, could not receive platinum, or had financial constraints, I would treat the patient with singe-agent intravenous chemotherapy or with oral metronomic chemotherapy, single-agent targeted therapy or with best supportive care,” she said.
Dr. Rischin has received research funding from Amgen, Bristol-Myers Squibb, Genentech/Roche, GSK, Merck, and Regeneron. Dr. Noronha has received research funding (to her institution) from Amgen,and Sanofi Aventis.
SOURCE: D Rischin et al., ASCO 2019: Abstract 6000.
REPORTING FROM ASCO 2019
Short-term ADT improves radiation salvage after prostatectomy
CHICAGO – Adding short-term androgen deprivation therapy (ADT) to radiotherapy as salvage treatment after radical prostatectomy was associated with significantly better metastasis-free survival at nearly 10 years compared with salvage radiation alone, long-term results of a randomized phase 3 trial show.
After a median follow-up of 112 months (9.3 years), the metastasis-free survival (MFS) rate for 369 patients assigned to receive salvage radiation and short-term goserelin was 75%, compared with 69% for 374 patients randomized to radiation alone (P = .034), reported Nicolas Magné, MD, from Jean Monnet Saint Etienne University in Saint-Priest en Jarez, France.
“We can conclude and do believe that short ADT, only two injections at 3-month intervals, could increase MFS at 10 years compared to radiation alone in patients with rising PSA after initial prostatectomy,“ he said at the annual meeting of the American Society of Clinical Oncology.
There was no significant difference, however, in the secondary endpoint of overall survival at 10 years.
Dr. Magné and co-investigators in the GETUG-AFU 16 trial had previously reported that after a median follow-up of 5.3 years, patients assigned to radiation plus goserelin were significantly more likely to be free of biochemical or clinical progression at 5 years than patients assigned to radiotherapy alone (80% vs, 62%, hazard ratio [HR] 0.50, P less than .0001).
The open-label trial enrolled men 18 or older from 43 French centers who had been treated for a histologically confirmed adenocarcinoma of the prostate but had not received prior androgen deprivation therapy (ADT) or pelvic radiation. The patients had either stage pT2 or pT3 cancers, or stage pT4a with invasive disease limited to the bladder neck. The patients all had biochemical failure, defined as a rising prostate-specific antigen (PSA) of 0.2 to 2.0 mcg/L following radical prostatectomy, with no clinically evident disease.
The patients were randomly assigned to receive standard salvage radiotherapy either alone or with hormonal therapy. Randomization was stratified by investigational site, radiotherapy modality, and prognosis.
Radiotherapy consisted of either 3-D conformal radiotherapy or intensity modulated radiotherapy, delivered in 66 Gy doses divided into 33 fractions of 2 Gy each 5 days a week for 7 weeks.
Patients assigned to hormonal therapy in addition to radiation received one subcutaneous injection of goserelin 10.8 mg on the first day of radiation, and a second injection 3 months later.
Progression-free survival (PFS), the primary endpoint, was significantly better with the combination than with radiation alone for both low-risk patients (HR 0.47, 95% confidence interval [CI] 0.28-0.80), and high-risk patients (HR 0.56, CI 0.44-0.83).
As noted before, metastasis-free survival was also significantly better in the combination arm ( HR, 0.73, P = .034) at 10 years.
Invited discussant Daniel Spratt, MD, from the University of Michigan in Ann Arbor, commented that the study results “do show, just like they did in 2016, that bicochemical control is improved, which is linked to their primary endpoint of PFS, but I always caution that this alone will always be improved with testosterone suppression.”
He noted that if you give ADT to patients with low-risk prostate cancer “that we don’t usually even treat today,” adding hormonal therapy will produce a nearly identical improvement in biochemical control, suggesting more of a signal than a clinical benefit.
The improvement in MFS, however, is indeed a clinical benefit, “but it is a small difference, and one thing to note is that when you give these patients about 6 months of hormonal therapy, depending on the age of the patient, it can be about 6 months until they recover testosterone, and at their median follow-up, you can see that the delay in MFS, which is usually the trigger to start hormone therapy, is about 12 months. So it’s important when you counsel these patients that [for] about potentially 6 months to a year of symptoms you may delay the need for hormone therapy by about 12 months,” he said.
The study was supported by UNICANCER and AstraZeneca. Dr. Magné reported no relevant disclosures. Dr. Spratt reported amconsulting or advisory role with Blue Earth Diagnostics and Janssen Oncology.
SOURCE: Magn é D et al. ASCO 2019. Abstract 5001.
CHICAGO – Adding short-term androgen deprivation therapy (ADT) to radiotherapy as salvage treatment after radical prostatectomy was associated with significantly better metastasis-free survival at nearly 10 years compared with salvage radiation alone, long-term results of a randomized phase 3 trial show.
After a median follow-up of 112 months (9.3 years), the metastasis-free survival (MFS) rate for 369 patients assigned to receive salvage radiation and short-term goserelin was 75%, compared with 69% for 374 patients randomized to radiation alone (P = .034), reported Nicolas Magné, MD, from Jean Monnet Saint Etienne University in Saint-Priest en Jarez, France.
“We can conclude and do believe that short ADT, only two injections at 3-month intervals, could increase MFS at 10 years compared to radiation alone in patients with rising PSA after initial prostatectomy,“ he said at the annual meeting of the American Society of Clinical Oncology.
There was no significant difference, however, in the secondary endpoint of overall survival at 10 years.
Dr. Magné and co-investigators in the GETUG-AFU 16 trial had previously reported that after a median follow-up of 5.3 years, patients assigned to radiation plus goserelin were significantly more likely to be free of biochemical or clinical progression at 5 years than patients assigned to radiotherapy alone (80% vs, 62%, hazard ratio [HR] 0.50, P less than .0001).
The open-label trial enrolled men 18 or older from 43 French centers who had been treated for a histologically confirmed adenocarcinoma of the prostate but had not received prior androgen deprivation therapy (ADT) or pelvic radiation. The patients had either stage pT2 or pT3 cancers, or stage pT4a with invasive disease limited to the bladder neck. The patients all had biochemical failure, defined as a rising prostate-specific antigen (PSA) of 0.2 to 2.0 mcg/L following radical prostatectomy, with no clinically evident disease.
The patients were randomly assigned to receive standard salvage radiotherapy either alone or with hormonal therapy. Randomization was stratified by investigational site, radiotherapy modality, and prognosis.
Radiotherapy consisted of either 3-D conformal radiotherapy or intensity modulated radiotherapy, delivered in 66 Gy doses divided into 33 fractions of 2 Gy each 5 days a week for 7 weeks.
Patients assigned to hormonal therapy in addition to radiation received one subcutaneous injection of goserelin 10.8 mg on the first day of radiation, and a second injection 3 months later.
Progression-free survival (PFS), the primary endpoint, was significantly better with the combination than with radiation alone for both low-risk patients (HR 0.47, 95% confidence interval [CI] 0.28-0.80), and high-risk patients (HR 0.56, CI 0.44-0.83).
As noted before, metastasis-free survival was also significantly better in the combination arm ( HR, 0.73, P = .034) at 10 years.
Invited discussant Daniel Spratt, MD, from the University of Michigan in Ann Arbor, commented that the study results “do show, just like they did in 2016, that bicochemical control is improved, which is linked to their primary endpoint of PFS, but I always caution that this alone will always be improved with testosterone suppression.”
He noted that if you give ADT to patients with low-risk prostate cancer “that we don’t usually even treat today,” adding hormonal therapy will produce a nearly identical improvement in biochemical control, suggesting more of a signal than a clinical benefit.
The improvement in MFS, however, is indeed a clinical benefit, “but it is a small difference, and one thing to note is that when you give these patients about 6 months of hormonal therapy, depending on the age of the patient, it can be about 6 months until they recover testosterone, and at their median follow-up, you can see that the delay in MFS, which is usually the trigger to start hormone therapy, is about 12 months. So it’s important when you counsel these patients that [for] about potentially 6 months to a year of symptoms you may delay the need for hormone therapy by about 12 months,” he said.
The study was supported by UNICANCER and AstraZeneca. Dr. Magné reported no relevant disclosures. Dr. Spratt reported amconsulting or advisory role with Blue Earth Diagnostics and Janssen Oncology.
SOURCE: Magn é D et al. ASCO 2019. Abstract 5001.
CHICAGO – Adding short-term androgen deprivation therapy (ADT) to radiotherapy as salvage treatment after radical prostatectomy was associated with significantly better metastasis-free survival at nearly 10 years compared with salvage radiation alone, long-term results of a randomized phase 3 trial show.
After a median follow-up of 112 months (9.3 years), the metastasis-free survival (MFS) rate for 369 patients assigned to receive salvage radiation and short-term goserelin was 75%, compared with 69% for 374 patients randomized to radiation alone (P = .034), reported Nicolas Magné, MD, from Jean Monnet Saint Etienne University in Saint-Priest en Jarez, France.
“We can conclude and do believe that short ADT, only two injections at 3-month intervals, could increase MFS at 10 years compared to radiation alone in patients with rising PSA after initial prostatectomy,“ he said at the annual meeting of the American Society of Clinical Oncology.
There was no significant difference, however, in the secondary endpoint of overall survival at 10 years.
Dr. Magné and co-investigators in the GETUG-AFU 16 trial had previously reported that after a median follow-up of 5.3 years, patients assigned to radiation plus goserelin were significantly more likely to be free of biochemical or clinical progression at 5 years than patients assigned to radiotherapy alone (80% vs, 62%, hazard ratio [HR] 0.50, P less than .0001).
The open-label trial enrolled men 18 or older from 43 French centers who had been treated for a histologically confirmed adenocarcinoma of the prostate but had not received prior androgen deprivation therapy (ADT) or pelvic radiation. The patients had either stage pT2 or pT3 cancers, or stage pT4a with invasive disease limited to the bladder neck. The patients all had biochemical failure, defined as a rising prostate-specific antigen (PSA) of 0.2 to 2.0 mcg/L following radical prostatectomy, with no clinically evident disease.
The patients were randomly assigned to receive standard salvage radiotherapy either alone or with hormonal therapy. Randomization was stratified by investigational site, radiotherapy modality, and prognosis.
Radiotherapy consisted of either 3-D conformal radiotherapy or intensity modulated radiotherapy, delivered in 66 Gy doses divided into 33 fractions of 2 Gy each 5 days a week for 7 weeks.
Patients assigned to hormonal therapy in addition to radiation received one subcutaneous injection of goserelin 10.8 mg on the first day of radiation, and a second injection 3 months later.
Progression-free survival (PFS), the primary endpoint, was significantly better with the combination than with radiation alone for both low-risk patients (HR 0.47, 95% confidence interval [CI] 0.28-0.80), and high-risk patients (HR 0.56, CI 0.44-0.83).
As noted before, metastasis-free survival was also significantly better in the combination arm ( HR, 0.73, P = .034) at 10 years.
Invited discussant Daniel Spratt, MD, from the University of Michigan in Ann Arbor, commented that the study results “do show, just like they did in 2016, that bicochemical control is improved, which is linked to their primary endpoint of PFS, but I always caution that this alone will always be improved with testosterone suppression.”
He noted that if you give ADT to patients with low-risk prostate cancer “that we don’t usually even treat today,” adding hormonal therapy will produce a nearly identical improvement in biochemical control, suggesting more of a signal than a clinical benefit.
The improvement in MFS, however, is indeed a clinical benefit, “but it is a small difference, and one thing to note is that when you give these patients about 6 months of hormonal therapy, depending on the age of the patient, it can be about 6 months until they recover testosterone, and at their median follow-up, you can see that the delay in MFS, which is usually the trigger to start hormone therapy, is about 12 months. So it’s important when you counsel these patients that [for] about potentially 6 months to a year of symptoms you may delay the need for hormone therapy by about 12 months,” he said.
The study was supported by UNICANCER and AstraZeneca. Dr. Magné reported no relevant disclosures. Dr. Spratt reported amconsulting or advisory role with Blue Earth Diagnostics and Janssen Oncology.
SOURCE: Magn é D et al. ASCO 2019. Abstract 5001.
REPORTING FROM ASCO 2019