Lung Cancer

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.

The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.

Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”

The study was published online in Nature Medicine.

A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.

The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.

TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.

The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.

“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.

The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.

Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.

One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.

“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.

This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.

“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.

In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment. 

The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.

“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
 

‘Yeoman’s effort’ paving the way forward

Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”

“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.

He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”

“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.

“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.

All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.

The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group.  A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.

The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.

Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”

The study was published online in Nature Medicine.

A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.

The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.

TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.

The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.

“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.

The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.

Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.

One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.

“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.

This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.

“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.

In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment. 

The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.

“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
 

‘Yeoman’s effort’ paving the way forward

Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”

“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.

He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”

“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.

“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.

All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.

The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group.  A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) led to complete and long-lasting responses in 2 of 16 patients with metastatic non-small cell lung cancer (NSCLC) who fully underwent the therapy in a phase 1 study.

The results are “very impressive, with two complete responses that are ongoing 1.5 years later, so it’s durable, and that’s encouraging,” Fred Hirsch, MD, PhD, director of the Center of Excellence for Thoracic Oncology at Mount Sinai’s Tisch Cancer Institute, New York, told this news organization.

Dr. Hirsch, who wasn’t involved in the research, also noted that this study is in immunotherapy-resistant metastatic lung cancer – “a situation where we actually don’t know exactly how best to treat it today.”

The study was published online in Nature Medicine.

A form of immunotherapy, TILs have been studied extensively in melanoma, as reported by this news organization, but this is the first test of the TIL therapy in metastatic NSCLC.

The single-arm, open-label phase 1 trial involved 20 patients who had TILs collected, including 16 who eventually received TILs. Median age was 54 years; all patients had metastatic NSCLC and disease progression after nivolumab monotherapy.

TILs cultured from an individual patient’s tumor were expanded ex vivo from minced tumors cultured with interleukin-2 (IL-2). Via this method, “billions of activated T cells can be produced and infused back into a patient,” explain the authors.

The full treatment regimen comprised cyclophosphamide and fludarabine lymphodepletion, TIL infusion and IL-2, followed by maintenance nivolumab.

“We found that infusion of TILs in combination with lymphodepletion and IL-2 had manageable toxicity and mediated tumor regressions in several patients, including complete responses,” report Benjamin Creelan, MD, of the Moffitt Cancer Center & Research Institute, Tampa, and colleagues.

The endpoint of safety was met according to the prespecified criteria of a rate of severe toxicity of 17% or less.

Among 13 evaluable patients, three had confirmed responses and 11 had reduction in tumor burden. Two patients achieved complete responses that were ongoing 1.5 years following TIL treatment.

One durable complete response occurred in a PD-L1-negative never-smoker, who had a low tumor mutation burden and who was refractory to nivolumab.

“This may be particularly encouraging for the large subset of never-smoker patients, for whom immune-checkpoint inhibitors have historically had limited efficacy,” the investigators say.

This complete responder had “features where you wouldn’t expect to see a response for immunotherapy,” Dr. Hirsch told this news organization.

“Low tumor mutation burden, negative PDL-1, and never-smoker are three factors which indicate some kind of resistance to immunotherapy, and despite that, there was a complete response with this specific therapy. That is fascinating,” he said.

In exploratory analyses, T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in patients who responded to treatment. 

The researchers say these early data indicate that TILs can mediate effective responses in tumor subtypes that are not sensitive to traditional immune-checkpoint-targeted therapy.

“Therefore, therapy with TILs may extend the scope and impact of immunotherapy into wider populations,” they write.
 

‘Yeoman’s effort’ paving the way forward

Also weighing in on the study, Philip Greenberg, MD, professor and head of immunology, Fred Hutchinson Cancer Center, Seattle, said, “In some respects, it’s quite promising and in other respects, actually more limited than you would hope for.”

“I think it’s a great demonstration that there is activity here, and there’s a world of things that can be done to improve the activity and no doubt that will be done. After this trial, I’m sure we will see next-generation trials,” said Dr. Greenberg.

He said key issues going forward are how cells are selected and manufactured: “That’s going to be a critical piece for making it better.”

“There is now a world of data that says T cells that recognize mutations in cancers can be effective in solid tumors,” Dr. Greenberg said.

“Sustaining that response is still a huge obstacle for achieving the kinds of therapeutic benefits we’d like to be achieved. And having that response be broad enough, particularly in the setting where most of the mutations are just passenger mutations, not driver oncogenes, is going to require a way of generating a large polyspecific population of cells that can persist for a long time,” he further commented.

All in all, this study was a “yeoman’s effort” and the researchers “deserve a lot of credit for pushing it forward,” Dr. Greenberg said.

The study was supported in part by grants from Stand Up to Cancer Foundation, the Barbara Bauer Prelude to a Cure Foundation, Iovance Biotherapeutics, and a Young Investigator award from Adaptive Biotechnologies. Nivolumab was supplied by Bristol-Myers Squibb. Aldesleukin (IL-2) was supplied by Clinigen Group.  A complete list of author disclosures is available with the original article. Dr. Hirsch and Dr. Greenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

A version of this article first appeared on Medscape.com.

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

A version of this article first appeared on Medscape.com.

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

A version of this article first appeared on Medscape.com.

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

A version of this article first appeared on Medscape.com.

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

A version of this article first appeared on Medscape.com.

One in three of the most popular news and feature articles on social media about the treatment of the four leading cancers in the United States contains misinformation, and the majority of those have the potential to harm patients, according to a new analysis.

Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.

Among these articles containing misinformation, 76.9% (50/65) contained harmful information.

“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.

“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.

“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”

The study was published online July 22 in the Journal of the National Cancer Institute.

The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.

Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.

One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.

The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.

“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.

Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.

“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.

Dr. Southwell recommends that clinicians be proactive about medical misinformation.

“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.

In short, ask patients what they know about the treatment of their cancer, he suggests.

“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
 

Study details

For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.

Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.

This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).

Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).

In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).

The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).

A limitation of the study is that it included only the most popular English language cancer articles.

This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.

A version of this article first appeared on Medscape.com.

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

rfranki@mdedge.com

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

rfranki@mdedge.com

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

rfranki@mdedge.com

Dr Mark A. Socinski, executive medical director of AdventHealth Cancer Institute in Orlando, Florida, highlights studies in advanced non–small cell lung cancer (NSCLC) presented at the 2021 annual meeting of the American Society of Clinical Oncology.
First, Dr Socinski reports on the updated results of the CheckMate 9LA study showing continued benefit of nivolumab and ipilimumab plus chemotherapy vs chemotherapy alone.

He also outlines an FDA pooled analysis of randomized controlled trials showing that patients with PD-L1 scores between 1% and 49% benefit most from immunotherapy plus chemotherapy compared with immunotherapy alone.

Dr Socinski then takes us through one of his own studies showing that immune-related adverse events are actually associated with better outcomes, and reports some sobering data from two studies suggesting that biomarker testing is lagging behind in NSCLC patients, especially among African Americans. He closes by reviewing updated results of the CodeBreak 100 trial which showed encouraging response to sotorasib among patients with G12C KRAS mutations.

--

Mark A. Socinski, MD, Executive Medical Director, AdventHealth Cancer Institute, Orlando, Florida.

Mark A. Socinski, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Genentech; Novartis; Guardant; AstraZeneca; Eli Lilly and Company; Blueprint
Received research grant from: Genentech; AstraZeneca; Novartis; Spectrum; Cullinan.

Dr Mark A. Socinski, executive medical director of AdventHealth Cancer Institute in Orlando, Florida, highlights studies in advanced non–small cell lung cancer (NSCLC) presented at the 2021 annual meeting of the American Society of Clinical Oncology.
First, Dr Socinski reports on the updated results of the CheckMate 9LA study showing continued benefit of nivolumab and ipilimumab plus chemotherapy vs chemotherapy alone.

He also outlines an FDA pooled analysis of randomized controlled trials showing that patients with PD-L1 scores between 1% and 49% benefit most from immunotherapy plus chemotherapy compared with immunotherapy alone.

Dr Socinski then takes us through one of his own studies showing that immune-related adverse events are actually associated with better outcomes, and reports some sobering data from two studies suggesting that biomarker testing is lagging behind in NSCLC patients, especially among African Americans. He closes by reviewing updated results of the CodeBreak 100 trial which showed encouraging response to sotorasib among patients with G12C KRAS mutations.

--

Mark A. Socinski, MD, Executive Medical Director, AdventHealth Cancer Institute, Orlando, Florida.

Mark A. Socinski, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Genentech; Novartis; Guardant; AstraZeneca; Eli Lilly and Company; Blueprint
Received research grant from: Genentech; AstraZeneca; Novartis; Spectrum; Cullinan.

Dr Mark A. Socinski, executive medical director of AdventHealth Cancer Institute in Orlando, Florida, highlights studies in advanced non–small cell lung cancer (NSCLC) presented at the 2021 annual meeting of the American Society of Clinical Oncology.
First, Dr Socinski reports on the updated results of the CheckMate 9LA study showing continued benefit of nivolumab and ipilimumab plus chemotherapy vs chemotherapy alone.

He also outlines an FDA pooled analysis of randomized controlled trials showing that patients with PD-L1 scores between 1% and 49% benefit most from immunotherapy plus chemotherapy compared with immunotherapy alone.

Dr Socinski then takes us through one of his own studies showing that immune-related adverse events are actually associated with better outcomes, and reports some sobering data from two studies suggesting that biomarker testing is lagging behind in NSCLC patients, especially among African Americans. He closes by reviewing updated results of the CodeBreak 100 trial which showed encouraging response to sotorasib among patients with G12C KRAS mutations.

--

Mark A. Socinski, MD, Executive Medical Director, AdventHealth Cancer Institute, Orlando, Florida.

Mark A. Socinski, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Genentech; Novartis; Guardant; AstraZeneca; Eli Lilly and Company; Blueprint
Received research grant from: Genentech; AstraZeneca; Novartis; Spectrum; Cullinan.

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

Using low-dose computed tomography (LDCT) to screen for aortic valve calcification during a lung cancer screening could identify those at risk for aortic stenosis, says new research published in Annals of Internal Medicine.

Aortic stenosis is one of the most common valve disease problems and is characterized by the narrowing of the aortic valve opening, according to the American Heart Association. The condition impedes the delivery of blood from the heart to the body.

Researchers found that LDCT, which according to the Centers for Disease Control and Prevention is the only recommended screening test for lung cancer, also can be used to identify aortic valve calcification – a condition in which calcium deposits form on the aortic valve, narrowing it.

Since cardiovascular events and lung cancer are known to have the same modifiable risk factors, people screened for lung cancer could also be diagnosed with cardiovascular diseases, the authors noted in their paper.

Furthermore, a 2019 study published in the Journal of Thoracic Imaging found that LDCT can be useful for identifying not just lung cancer, but the early stages of chronic obstructive pulmonary disease and coronary artery disease.

“LDCT has been described as useful for identifying the early stages of chronic obstructive pulmonary disease and coronary artery disease, but it can also [screen for] calcified aortic valve [which corresponds] with the risk of severe aortic stenosis,” study author Marcin Fijalkowski, MD, PhD, of the Medical University of Gdansk, said in an interview. “This additional evaluation is not time-consuming and is easy to perform.”
 

Methods and results

For the study, Dr. Fijalkowski and his colleagues examined data from 6,631 people between the ages of 50 and 80 years of age with a smoking history of 30 or more pack-years. The group was enrolled in the MOLTEST BIS lung cancer screening program between 2016 and 2018, which assessed the usefulness of LDCT performed during lung cancer screening in determining the degree of aortic valve calcification as an additional finding. The researchers arbitrarily determined a calcium score of 900 as a cutoff point indicating a positive test result. Positive patients were sent for an echocardiogram for confirmation of diagnosis.

Aortic valve calcification was identified in 869 patients, 13.1% of the group. Sixty-eight participants, which is about 8% of this group, were identified as having a calcium score of 900 at least and were referred for echocardiography to confirm these results. Of this group, 0.5% were diagnosed with at least moderate aortic stenosis after receiving an echocardiogram. About 55% of the participants with this condition were unaware of their valvular heart disease, including 23% with a severe form of the disease.
 

Study identified patients who had not been aware of disease

Dr. Fijalkowski said while he was not surprised by the findings, he was surprised that the study may have saved some of the participants’ lives.

“We were expecting the same degree of calcification of aortic valve and correlation with aortic stenosis severity, but what surprised us was that half of diagnosed patients were not aware of disease,” he said. “This additional finding was lifesaving.”

In the paper, the authors noted that cardiology societies do not yet recognize LDCT as a diagnostic tool for aortic stenosis. Based on their findings, they propose that aortic valve calcification become a routine assessment procedure in the LDCT protocol for lung cancer screening.
 

Findings are ‘important’ but not practice changing

Salim S. Virani, MD, FACC, who was not involved in the study, said this new research is important.

The analyses were done well and push the needle further in a direction that suggests “when we are doing imaging for one reason, we should use the totality of information that we have available,” he noted.

“I mean, if you are looking at a lung nodule, if you see an aortic valve that’s very calcified, then it should prompt you to at least ask the patient about some symptoms related to that,” Dr. Virani explained.

However, he said more research is needed on a larger population before LDCT can be considered a diagnostic tool for aortic stenosis.

“I think we have to understand that this study was done in a very specific group of patients,” said Dr. Virani, professor in the sections of cardiology and cardiovascular research at Baylor College of Medicine, Houston. “If you were to do it in a population that was much younger, with much lower risk of even lung cancer, then the yield of a CT to pick up aortic stenosis would be lower.”

Before any practice changes are made regarding LDCT and the diagnosis of aortic stenosis, there needs to be more research on how many people in the general population are getting non–cardiology-related chest imaging and then come up with a population-based metric as to what calcium score cutoff could be used, he said.

Dr. Fijalkowski said he believes the results of his study will encourage physicians to focus not only on pulmonary nodules but also to look for additional things such as aortic valve calcification.

The experts did not disclose any relevant financial relationships.

Using low-dose computed tomography (LDCT) to screen for aortic valve calcification during a lung cancer screening could identify those at risk for aortic stenosis, says new research published in Annals of Internal Medicine.

Aortic stenosis is one of the most common valve disease problems and is characterized by the narrowing of the aortic valve opening, according to the American Heart Association. The condition impedes the delivery of blood from the heart to the body.

Researchers found that LDCT, which according to the Centers for Disease Control and Prevention is the only recommended screening test for lung cancer, also can be used to identify aortic valve calcification – a condition in which calcium deposits form on the aortic valve, narrowing it.

Since cardiovascular events and lung cancer are known to have the same modifiable risk factors, people screened for lung cancer could also be diagnosed with cardiovascular diseases, the authors noted in their paper.

Furthermore, a 2019 study published in the Journal of Thoracic Imaging found that LDCT can be useful for identifying not just lung cancer, but the early stages of chronic obstructive pulmonary disease and coronary artery disease.

“LDCT has been described as useful for identifying the early stages of chronic obstructive pulmonary disease and coronary artery disease, but it can also [screen for] calcified aortic valve [which corresponds] with the risk of severe aortic stenosis,” study author Marcin Fijalkowski, MD, PhD, of the Medical University of Gdansk, said in an interview. “This additional evaluation is not time-consuming and is easy to perform.”
 

Methods and results

For the study, Dr. Fijalkowski and his colleagues examined data from 6,631 people between the ages of 50 and 80 years of age with a smoking history of 30 or more pack-years. The group was enrolled in the MOLTEST BIS lung cancer screening program between 2016 and 2018, which assessed the usefulness of LDCT performed during lung cancer screening in determining the degree of aortic valve calcification as an additional finding. The researchers arbitrarily determined a calcium score of 900 as a cutoff point indicating a positive test result. Positive patients were sent for an echocardiogram for confirmation of diagnosis.

Aortic valve calcification was identified in 869 patients, 13.1% of the group. Sixty-eight participants, which is about 8% of this group, were identified as having a calcium score of 900 at least and were referred for echocardiography to confirm these results. Of this group, 0.5% were diagnosed with at least moderate aortic stenosis after receiving an echocardiogram. About 55% of the participants with this condition were unaware of their valvular heart disease, including 23% with a severe form of the disease.
 

Study identified patients who had not been aware of disease

Dr. Fijalkowski said while he was not surprised by the findings, he was surprised that the study may have saved some of the participants’ lives.

“We were expecting the same degree of calcification of aortic valve and correlation with aortic stenosis severity, but what surprised us was that half of diagnosed patients were not aware of disease,” he said. “This additional finding was lifesaving.”

In the paper, the authors noted that cardiology societies do not yet recognize LDCT as a diagnostic tool for aortic stenosis. Based on their findings, they propose that aortic valve calcification become a routine assessment procedure in the LDCT protocol for lung cancer screening.
 

Findings are ‘important’ but not practice changing

Salim S. Virani, MD, FACC, who was not involved in the study, said this new research is important.

The analyses were done well and push the needle further in a direction that suggests “when we are doing imaging for one reason, we should use the totality of information that we have available,” he noted.

“I mean, if you are looking at a lung nodule, if you see an aortic valve that’s very calcified, then it should prompt you to at least ask the patient about some symptoms related to that,” Dr. Virani explained.

However, he said more research is needed on a larger population before LDCT can be considered a diagnostic tool for aortic stenosis.

“I think we have to understand that this study was done in a very specific group of patients,” said Dr. Virani, professor in the sections of cardiology and cardiovascular research at Baylor College of Medicine, Houston. “If you were to do it in a population that was much younger, with much lower risk of even lung cancer, then the yield of a CT to pick up aortic stenosis would be lower.”

Before any practice changes are made regarding LDCT and the diagnosis of aortic stenosis, there needs to be more research on how many people in the general population are getting non–cardiology-related chest imaging and then come up with a population-based metric as to what calcium score cutoff could be used, he said.

Dr. Fijalkowski said he believes the results of his study will encourage physicians to focus not only on pulmonary nodules but also to look for additional things such as aortic valve calcification.

The experts did not disclose any relevant financial relationships.

Using low-dose computed tomography (LDCT) to screen for aortic valve calcification during a lung cancer screening could identify those at risk for aortic stenosis, says new research published in Annals of Internal Medicine.

Aortic stenosis is one of the most common valve disease problems and is characterized by the narrowing of the aortic valve opening, according to the American Heart Association. The condition impedes the delivery of blood from the heart to the body.

Researchers found that LDCT, which according to the Centers for Disease Control and Prevention is the only recommended screening test for lung cancer, also can be used to identify aortic valve calcification – a condition in which calcium deposits form on the aortic valve, narrowing it.

Since cardiovascular events and lung cancer are known to have the same modifiable risk factors, people screened for lung cancer could also be diagnosed with cardiovascular diseases, the authors noted in their paper.

Furthermore, a 2019 study published in the Journal of Thoracic Imaging found that LDCT can be useful for identifying not just lung cancer, but the early stages of chronic obstructive pulmonary disease and coronary artery disease.

“LDCT has been described as useful for identifying the early stages of chronic obstructive pulmonary disease and coronary artery disease, but it can also [screen for] calcified aortic valve [which corresponds] with the risk of severe aortic stenosis,” study author Marcin Fijalkowski, MD, PhD, of the Medical University of Gdansk, said in an interview. “This additional evaluation is not time-consuming and is easy to perform.”
 

Methods and results

For the study, Dr. Fijalkowski and his colleagues examined data from 6,631 people between the ages of 50 and 80 years of age with a smoking history of 30 or more pack-years. The group was enrolled in the MOLTEST BIS lung cancer screening program between 2016 and 2018, which assessed the usefulness of LDCT performed during lung cancer screening in determining the degree of aortic valve calcification as an additional finding. The researchers arbitrarily determined a calcium score of 900 as a cutoff point indicating a positive test result. Positive patients were sent for an echocardiogram for confirmation of diagnosis.

Aortic valve calcification was identified in 869 patients, 13.1% of the group. Sixty-eight participants, which is about 8% of this group, were identified as having a calcium score of 900 at least and were referred for echocardiography to confirm these results. Of this group, 0.5% were diagnosed with at least moderate aortic stenosis after receiving an echocardiogram. About 55% of the participants with this condition were unaware of their valvular heart disease, including 23% with a severe form of the disease.
 

Study identified patients who had not been aware of disease

Dr. Fijalkowski said while he was not surprised by the findings, he was surprised that the study may have saved some of the participants’ lives.

“We were expecting the same degree of calcification of aortic valve and correlation with aortic stenosis severity, but what surprised us was that half of diagnosed patients were not aware of disease,” he said. “This additional finding was lifesaving.”

In the paper, the authors noted that cardiology societies do not yet recognize LDCT as a diagnostic tool for aortic stenosis. Based on their findings, they propose that aortic valve calcification become a routine assessment procedure in the LDCT protocol for lung cancer screening.
 

Findings are ‘important’ but not practice changing

Salim S. Virani, MD, FACC, who was not involved in the study, said this new research is important.

The analyses were done well and push the needle further in a direction that suggests “when we are doing imaging for one reason, we should use the totality of information that we have available,” he noted.

“I mean, if you are looking at a lung nodule, if you see an aortic valve that’s very calcified, then it should prompt you to at least ask the patient about some symptoms related to that,” Dr. Virani explained.

However, he said more research is needed on a larger population before LDCT can be considered a diagnostic tool for aortic stenosis.

“I think we have to understand that this study was done in a very specific group of patients,” said Dr. Virani, professor in the sections of cardiology and cardiovascular research at Baylor College of Medicine, Houston. “If you were to do it in a population that was much younger, with much lower risk of even lung cancer, then the yield of a CT to pick up aortic stenosis would be lower.”

Before any practice changes are made regarding LDCT and the diagnosis of aortic stenosis, there needs to be more research on how many people in the general population are getting non–cardiology-related chest imaging and then come up with a population-based metric as to what calcium score cutoff could be used, he said.

Dr. Fijalkowski said he believes the results of his study will encourage physicians to focus not only on pulmonary nodules but also to look for additional things such as aortic valve calcification.

The experts did not disclose any relevant financial relationships.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A simple nasal swab may help in the diagnosis of lung cancer in smokers who have undergone CT screening and had lung nodules detected on the scan.  

Only about 5% of the nearly 1.6 million lung nodules identified as incidental findings on low-dose CT screening tests will turn out to be malignant. The new test helps to distinguish between benign and malignant nodules, say researchers reporting a validation study.  

The results show that the test identified those at low risk for cancer with a sensitivity of 96.3% and specificity of 41.7%, as well as identifying those as high risk, with a specificity of 90.4% and sensitivity of 58.2%.

The Percepta nasal swab is a first-of-its-kind genomic test, says the manufacturer Veracyte.

It is based on “field of injury” technology, which examines genomic changes in the lining of the respiratory tract for evidence of active cancer cells, coupled with a machine learning model that includes factors such as age, gender, and smoking history.

Veracyte hopes to begin to make the test available to a select number of sites in the second half of 2021. “The test is intended to be performed in the physician’s office on patients referred with suspicious lung nodules found on CT scans,” said Giulia C. Kennedy, PhD, chief scientific officer and chief medical officer at Veracyte. “This could include patients with nodules found through screening programs, as well as incidentally.”

“It will be made available as a laboratory developed test in the U.S. through Veracyte’s centralized CLIA laboratory,” she said in an interview. “In global markets, we will offer the test as an IVD product that can be performed on the nCounter instrument by laboratories locally. Outside of the United States, the test will require a CE mark, which we are equipped to support.”

Results with the test were presented during the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, which was held virtually this year.

It was first tested in a training set, which consisted of more than 1,100 patients. All were current or former smokers who had a lung nodule detected on chest CT scanning and were followed for up to 1 year or until a final diagnosis of lung cancer or benign disease.

Brushings of the nasal epithelium were prospectively collected in patients with lung nodules from multiple cohorts.

A total of 502 genes were used in the classifier, and performance was evaluated in an independent clinical validation set consisting of 249 patients.

The test identified true benign patients as low risk with 41.7% specificity and 96.3% sensitivity, resulting in a negative predictive value (NPV) of 97.1% in a population with a cancer prevalence of 25%. The risk of malignancy for patients in this low-risk group was less than 3% (1-NPV), and for this group, clinical guidelines recommend surveillance.  

Patients with true malignancies were identified as high risk, with 58.2% sensitivity and 90.4% specificity, resulting in a positive predictive value of 67.0% in a population with 25% cancer prevalence. The risk of malignancy for patients deemed to be high risk by the classifier was 67.0%, which exceeds the current guideline threshold for consideration of surgical resection or other ablative therapy if a staging evaluation confirms early stage disease, the authors point out.  

The remaining patients, who did not meet the stringent cut-offs for low or high risk, were identified as intermediate risk. In this population, the prevalence of malignancy for patients identified as intermediate risk was 20.7%, which is consistent with guidelines that provide a range for intermediate-risk patients as between 5% and 65% for whom diagnostic biopsy is recommended.
 

Help guide decisions, more data needed

Approached by this news organization for independent comment, Alexander Spira, MD, PhD, medical oncologist, Virginia Cancer Specialists, Fairfax, explained that the study provides an interesting way to look at a common finding and lung nodules and to predict whether further workup should be done.

“This could provide a role in reassurance that patients who fall into the low-risk category could be observed with serial imaging rather than proceeding to immediate biopsy,” he said. “It falls in under the ‘field of injury’ principle.”

Dr. Spira noted that although the low-risk group appears to have a negative predictive value of >90%, it doesn’t mean that the patient would require no further workup. “It would require CT surveillance rather than proceeding to immediate biopsy, and at this point it does appear promising, but I would want further follow-up in terms of outcomes,” he said.

“This does not apply to nonsmokers, which is of increasing prevalence, but with the increased use of CT screening for patients with a history of tobacco use, it may indeed have a role.”

He also pointed out that while the idea is to avoid biopsies, the smaller lesions are the ones that are concerning. “They are often tough to get at, and it would also depend on patient choice and anxiety as well, given the chance of being in that low percentage that the test misses,” said Dr. Spira. “Lastly, many pulmonologists are ordering PET scans in lieu of a biopsy, and this may also help.”

The bottom line is that this may help guide clinical decisions, but more data are needed. “Even in the low-risk category, 9.4% of patients had a malignancy, which is still a high miss rate,” he added.

The study was funded by Veracyte. Dr. Kennedy is employed by Veracyte. Dr. Spira has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Lung cancer patients could soon have their risk of dying over the following 3 months accurately predicted by analyzing their urine samples, allowing them to better prepare for their end of life, say U.K. researchers.

Dr. Seamus Coyle, consultant in palliative medicine, the Clatterbridge Cancer Centre, Liverpool, and colleagues studied urine samples from more than 100 lung cancer patients, deriving a model based on their metabolite profile.

This allowed patients to be divided into high- and low-risk groups for dying over the following 3 months, with an accuracy of 88%.

The model “predicts dying … for every single day for the last 3 months of life,” Dr. Coyle said.

“That’s an outstanding prediction,” Dr. Coyle added, “based on the fact that people actively die over 2 to 3 days on average,” while “some die over a day.”

He continued: “It’s the only test that predicts dying within the last 2 weeks of life, and that’s what I’m passionate about: The earlier recognition of dying.”

The research was presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 4.
 

‘Promising and important pilot study’

Dr. Nathan Pennell, an ASCO expert, told this news organization that “predicting the actual ‘time’ someone has left is more of an art than a science.”

“For people who may be closer to death, this would potentially allow more focus on supportive care and allow families and patients to plan more accurately for supporting their loved one through the dying process.”

He continued that “while this is a promising and important pilot study, there is more work to be done before this could be used in practice.”

For example, the treatment status of the patients was not clear.

“Were these patients all in hospice, or were some undergoing treatment which, if effective, could ‘rescue’ them from their poor prognostic state?”

Dr. Pennell continued: “Would measuring kidney function be just as good? Is this something that could be intervened upon?

“For example, if someone has a high-risk score for dying, could medical intervention to treat an infection or some other modifiable action change that ‘fate’?”
 

Death ‘difficult to predict’

Dr. Coyle began by saying that, while for him recognizing that a patient is dying is the start of good end of life care, “recognizing dying accurately, when someone is in the last days of life, is difficult.”

He noted that the 2019 National Audit of Care at the End of Life found that people were recognized to be dying at median of 34 hours before death, with 20% recognized in the last 8 hours.

Moreover, 50% of people who are dying “are unconscious and unable to be involved in any conversation that [is] pertinent to them.”

In an attempt to better predict the onset of dying, the researchers conducted a prospective, longitudinal study in which 424 urine samples were collected from 162 lung cancer patients from six centers.

Of those, 63 patients gave a sample within the last 28 days of life, and 29 within the last week of life.

Urine samples were analyzed using a liquid chromatography quadrupole time-of-flight mass spectrometer for 112 patients, who had a median age of 71 years and a range of 47-89 years, and 40.2% were female. The most common diagnosis was non–small cell lung cancer, in 55.4%, while 19.6% had small cell lung cancer.

Performing Cox Lasso regression analysis on the “hundreds of metabolites” identified in the urine samples, the team developed an End of Life Metabolome (ELM) that predicted an individual’s risk of dying over the following 3 months.

Kaplan-Meier analysis allowed the patients to be divided into five risk groups based on their ELM (P < .001 for trend), which showed that all patients in the lowest-risk group were still alive after more than 2 months following the urine sample.

In contrast, more than 50% of patients in the highest-risk group died within 1 week of their urine sample being taken, and 100% had died within 3 weeks.

Calculating the area under the receiver operating characteristic curve revealed that the ELM was able to predict the risk of dying for every day for the last 3 months of life with an accuracy of 88%.

ELM is being validated in a new cohort of lung cancer patients and it is being assessed in multiple cancers.

The study was funded by the Wellcome Trust UK and North West Cancer Research UK.

No relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.