Lung Cancer

A cell-free DNA (cfDNA) test, or “liquid biopsy,” identifies more biomarkers and does so more quickly than tissue-based genotyping for guiding treatment in newly diagnosed advanced non–small cell lung cancer (NSCLC), according to a finding from a prospective study.

In 282 patients with newly diagnosed advanced NSCLC who were enrolled in the multicenter Noninvasive versus Invasive Lung Evaluation (NILE) study between July 2016 and April 2018, the “well-validated, comprehensive, and highly sensitive test” – Guardant360 – detected at least one guideline-recommended biomarker mutation in significantly more cases than did tissue-based tests alone (77 vs. 60 patients), Vassiliki A. Papadimitrakopoulou, MD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research annual meeting in Atlanta.

“Additionally, the cfDNA results were delivered significantly faster than the standard-of-care tissue results [median, 9 vs. 15 days],” said Dr. Papadimitrakopoulou, chief of the section of thoracic medical oncology and the Jay and Lori Eisenberg Distinguished Professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.


Guardant360 assesses for all guideline-recommended genomic biomarkers, Dr. Papadimitrakopoulou said, noting that nine such biomarkers have been identified. All biomarkers identified using the liquid biopsy were also detected in tissue every time.

“Plasma cfDNA testing therefore had 100% positive predictive value,” she said.

This is important, because “we know that about 30% of patients with newly diagnosed advanced non–small lung cancer have therapeutically targetable genomic alterations that make them eligible for targeted therapies,” she said.

“Identifying these patients is important, as the response rate to the properly identified targeted therapy is higher than response rates to first-line chemotherapy or immune checkpoint inhibitor therapy,” she added, explaining that tissue-based assessment has long been the standard of care option for identifying genomic biomarkers, but is limited by the risks associated with the biopsy procedure, the inability to test for all relevant mutations, and the time it takes – up to 30 days – to obtain results.

“[The NILE] results have very exciting implications for clinical practice, especially in light of the expanding list of genomic biomarkers to be assessed,” she said, concluding that the findings from NILE – the largest study of newly diagnosed advanced NSCLC – demonstrate that the clinical utility of this well-validated, comprehensive, sensitive cfDNA test “is cardinal in identification of patients with guideline-recommended biomarker-positive tumors, and it is an alternative to SOC [standard of care] tissue testing in the first-line testing.”

Clinical follow-up of patients is ongoing, she noted.

This study was funded by Guardant Health. Dr. Papadimitrakopoulou serves on the advisory boards of several pharmaceutical companies. She reported receiving CME speaker fees from F. Hoffmann–La Roche, and has received research support from Eli Lilly, Novartis, Merck, AstraZeneca, F. Hoffmann–La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte and Guardant Health.

SOURCE: Papadimitrakopoulou VA et al. AACR 2019, Abstract 4460..

A cell-free DNA (cfDNA) test, or “liquid biopsy,” identifies more biomarkers and does so more quickly than tissue-based genotyping for guiding treatment in newly diagnosed advanced non–small cell lung cancer (NSCLC), according to a finding from a prospective study.

In 282 patients with newly diagnosed advanced NSCLC who were enrolled in the multicenter Noninvasive versus Invasive Lung Evaluation (NILE) study between July 2016 and April 2018, the “well-validated, comprehensive, and highly sensitive test” – Guardant360 – detected at least one guideline-recommended biomarker mutation in significantly more cases than did tissue-based tests alone (77 vs. 60 patients), Vassiliki A. Papadimitrakopoulou, MD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research annual meeting in Atlanta.

“Additionally, the cfDNA results were delivered significantly faster than the standard-of-care tissue results [median, 9 vs. 15 days],” said Dr. Papadimitrakopoulou, chief of the section of thoracic medical oncology and the Jay and Lori Eisenberg Distinguished Professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.


Guardant360 assesses for all guideline-recommended genomic biomarkers, Dr. Papadimitrakopoulou said, noting that nine such biomarkers have been identified. All biomarkers identified using the liquid biopsy were also detected in tissue every time.

“Plasma cfDNA testing therefore had 100% positive predictive value,” she said.

This is important, because “we know that about 30% of patients with newly diagnosed advanced non–small lung cancer have therapeutically targetable genomic alterations that make them eligible for targeted therapies,” she said.

“Identifying these patients is important, as the response rate to the properly identified targeted therapy is higher than response rates to first-line chemotherapy or immune checkpoint inhibitor therapy,” she added, explaining that tissue-based assessment has long been the standard of care option for identifying genomic biomarkers, but is limited by the risks associated with the biopsy procedure, the inability to test for all relevant mutations, and the time it takes – up to 30 days – to obtain results.

“[The NILE] results have very exciting implications for clinical practice, especially in light of the expanding list of genomic biomarkers to be assessed,” she said, concluding that the findings from NILE – the largest study of newly diagnosed advanced NSCLC – demonstrate that the clinical utility of this well-validated, comprehensive, sensitive cfDNA test “is cardinal in identification of patients with guideline-recommended biomarker-positive tumors, and it is an alternative to SOC [standard of care] tissue testing in the first-line testing.”

Clinical follow-up of patients is ongoing, she noted.

This study was funded by Guardant Health. Dr. Papadimitrakopoulou serves on the advisory boards of several pharmaceutical companies. She reported receiving CME speaker fees from F. Hoffmann–La Roche, and has received research support from Eli Lilly, Novartis, Merck, AstraZeneca, F. Hoffmann–La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte and Guardant Health.

SOURCE: Papadimitrakopoulou VA et al. AACR 2019, Abstract 4460..

A cell-free DNA (cfDNA) test, or “liquid biopsy,” identifies more biomarkers and does so more quickly than tissue-based genotyping for guiding treatment in newly diagnosed advanced non–small cell lung cancer (NSCLC), according to a finding from a prospective study.

In 282 patients with newly diagnosed advanced NSCLC who were enrolled in the multicenter Noninvasive versus Invasive Lung Evaluation (NILE) study between July 2016 and April 2018, the “well-validated, comprehensive, and highly sensitive test” – Guardant360 – detected at least one guideline-recommended biomarker mutation in significantly more cases than did tissue-based tests alone (77 vs. 60 patients), Vassiliki A. Papadimitrakopoulou, MD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research annual meeting in Atlanta.

“Additionally, the cfDNA results were delivered significantly faster than the standard-of-care tissue results [median, 9 vs. 15 days],” said Dr. Papadimitrakopoulou, chief of the section of thoracic medical oncology and the Jay and Lori Eisenberg Distinguished Professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.


Guardant360 assesses for all guideline-recommended genomic biomarkers, Dr. Papadimitrakopoulou said, noting that nine such biomarkers have been identified. All biomarkers identified using the liquid biopsy were also detected in tissue every time.

“Plasma cfDNA testing therefore had 100% positive predictive value,” she said.

This is important, because “we know that about 30% of patients with newly diagnosed advanced non–small lung cancer have therapeutically targetable genomic alterations that make them eligible for targeted therapies,” she said.

“Identifying these patients is important, as the response rate to the properly identified targeted therapy is higher than response rates to first-line chemotherapy or immune checkpoint inhibitor therapy,” she added, explaining that tissue-based assessment has long been the standard of care option for identifying genomic biomarkers, but is limited by the risks associated with the biopsy procedure, the inability to test for all relevant mutations, and the time it takes – up to 30 days – to obtain results.

“[The NILE] results have very exciting implications for clinical practice, especially in light of the expanding list of genomic biomarkers to be assessed,” she said, concluding that the findings from NILE – the largest study of newly diagnosed advanced NSCLC – demonstrate that the clinical utility of this well-validated, comprehensive, sensitive cfDNA test “is cardinal in identification of patients with guideline-recommended biomarker-positive tumors, and it is an alternative to SOC [standard of care] tissue testing in the first-line testing.”

Clinical follow-up of patients is ongoing, she noted.

This study was funded by Guardant Health. Dr. Papadimitrakopoulou serves on the advisory boards of several pharmaceutical companies. She reported receiving CME speaker fees from F. Hoffmann–La Roche, and has received research support from Eli Lilly, Novartis, Merck, AstraZeneca, F. Hoffmann–La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte and Guardant Health.

SOURCE: Papadimitrakopoulou VA et al. AACR 2019, Abstract 4460..

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

mlesney@mdedge.com

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

Immune checkpoint inhibitors are safe and effective in HIV-infected patients with advanced cancers, according to authors of a recently published systematic review.

The treatment was well tolerated and associated with a 9% rate of grade 3 or higher immune-related adverse events, according to results of the review of 73 patient cases.

There were no adverse impacts on HIV load or CD4 cell count detected in the patients, according to researchers Michael R. Cook, MD, and Chul Kim, MD, MPH, of Georgetown University, Washington.

Antitumor activity of the checkpoint inhibitors in lung cancer patients was comparable to what has been seen in previous randomized clinical trials that excluded HIV-infected individuals, Dr. Cook and Dr. Kim reported in JAMA Oncology.

“Based on the results of the present systematic review, and in the absence of definitive prospective data suggesting an unfavorable risk-to-benefit ratio, immune checkpoint inhibitor therapy may be considered as a viable treatment option for HIV-infected patients with advanced cancer,” they said.

There are preclinical data suggesting that immune checkpoint modulation could improve function of HIV-specific T cells, the investigators added.

“Prospective trials of immune checkpoint inhibitors are necessary to elucidate the antiviral efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and cancer,” they said.

Several such trials are underway to evaluate the role of the pembrolizumab, nivolumab, nivolumab plus ipilimumab, and durvalumab in HIV-infected patients with advanced-stage cancers, according to the review authors.

In the present systematic review, Dr. Cook and Dr. Kim conducted a literature search and reviewed presentations from major annual medical conferences.

Of the 73 HIV-infected patients they identified, most had non–small cell lung cancer (34.2%), melanoma (21.9%), or Kaposi sarcoma (12.3%), while the rest had anal cancer, head and neck cancer, or other malignancies. Most patients had received either nivolumab (39.7%) or pembrolizumab (35.6%).

There were “no concerning findings” among these patients with regard to immune-mediated toxicities or changes in HIV-related parameters.

Six of 70 patients had immune-related adverse events of grade 3 or greater.

Thirty-four patients had documented HIV loads before and after receiving an immune checkpoint inhibitor. Of those, 28 had undetectable HIV loads at baseline, and all but 2 (7%) maintained undetectable loads in the posttreatment evaluation.

Of the remaining six with detectable HIV loads before treatment, five had a decrease in viral load, to the point that four had undetectable HIV viral load in the posttreatment evaluation, the investigators reported.

The overall response rate was 30% for the lung cancer patients, 27% for melanoma, and 63% for Kaposi sarcoma.

In the non–small cell lung cancer subset, response rates were 26% for those who had received previous systemic treatment, and 50% for those who had not, which was similar to findings from major checkpoint inhibitor trials that excluded HIV-infected individuals, the investigators said.

The American Society of Clinical Oncology Conquer Cancer Foundation and Georgetown University supported the study. Dr. Kim reported disclosures related to CARIS Life Science and AstraZeneca.

SOURCE: Cook MR and Kim C. JAMA Oncol. 2019 Feb 7. doi: 10.1001/jamaoncol.2018.6737.

Immune checkpoint inhibitors are safe and effective in HIV-infected patients with advanced cancers, according to authors of a recently published systematic review.

The treatment was well tolerated and associated with a 9% rate of grade 3 or higher immune-related adverse events, according to results of the review of 73 patient cases.

There were no adverse impacts on HIV load or CD4 cell count detected in the patients, according to researchers Michael R. Cook, MD, and Chul Kim, MD, MPH, of Georgetown University, Washington.

Antitumor activity of the checkpoint inhibitors in lung cancer patients was comparable to what has been seen in previous randomized clinical trials that excluded HIV-infected individuals, Dr. Cook and Dr. Kim reported in JAMA Oncology.

“Based on the results of the present systematic review, and in the absence of definitive prospective data suggesting an unfavorable risk-to-benefit ratio, immune checkpoint inhibitor therapy may be considered as a viable treatment option for HIV-infected patients with advanced cancer,” they said.

There are preclinical data suggesting that immune checkpoint modulation could improve function of HIV-specific T cells, the investigators added.

“Prospective trials of immune checkpoint inhibitors are necessary to elucidate the antiviral efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and cancer,” they said.

Several such trials are underway to evaluate the role of the pembrolizumab, nivolumab, nivolumab plus ipilimumab, and durvalumab in HIV-infected patients with advanced-stage cancers, according to the review authors.

In the present systematic review, Dr. Cook and Dr. Kim conducted a literature search and reviewed presentations from major annual medical conferences.

Of the 73 HIV-infected patients they identified, most had non–small cell lung cancer (34.2%), melanoma (21.9%), or Kaposi sarcoma (12.3%), while the rest had anal cancer, head and neck cancer, or other malignancies. Most patients had received either nivolumab (39.7%) or pembrolizumab (35.6%).

There were “no concerning findings” among these patients with regard to immune-mediated toxicities or changes in HIV-related parameters.

Six of 70 patients had immune-related adverse events of grade 3 or greater.

Thirty-four patients had documented HIV loads before and after receiving an immune checkpoint inhibitor. Of those, 28 had undetectable HIV loads at baseline, and all but 2 (7%) maintained undetectable loads in the posttreatment evaluation.

Of the remaining six with detectable HIV loads before treatment, five had a decrease in viral load, to the point that four had undetectable HIV viral load in the posttreatment evaluation, the investigators reported.

The overall response rate was 30% for the lung cancer patients, 27% for melanoma, and 63% for Kaposi sarcoma.

In the non–small cell lung cancer subset, response rates were 26% for those who had received previous systemic treatment, and 50% for those who had not, which was similar to findings from major checkpoint inhibitor trials that excluded HIV-infected individuals, the investigators said.

The American Society of Clinical Oncology Conquer Cancer Foundation and Georgetown University supported the study. Dr. Kim reported disclosures related to CARIS Life Science and AstraZeneca.

SOURCE: Cook MR and Kim C. JAMA Oncol. 2019 Feb 7. doi: 10.1001/jamaoncol.2018.6737.

Immune checkpoint inhibitors are safe and effective in HIV-infected patients with advanced cancers, according to authors of a recently published systematic review.

The treatment was well tolerated and associated with a 9% rate of grade 3 or higher immune-related adverse events, according to results of the review of 73 patient cases.

There were no adverse impacts on HIV load or CD4 cell count detected in the patients, according to researchers Michael R. Cook, MD, and Chul Kim, MD, MPH, of Georgetown University, Washington.

Antitumor activity of the checkpoint inhibitors in lung cancer patients was comparable to what has been seen in previous randomized clinical trials that excluded HIV-infected individuals, Dr. Cook and Dr. Kim reported in JAMA Oncology.

“Based on the results of the present systematic review, and in the absence of definitive prospective data suggesting an unfavorable risk-to-benefit ratio, immune checkpoint inhibitor therapy may be considered as a viable treatment option for HIV-infected patients with advanced cancer,” they said.

There are preclinical data suggesting that immune checkpoint modulation could improve function of HIV-specific T cells, the investigators added.

“Prospective trials of immune checkpoint inhibitors are necessary to elucidate the antiviral efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and cancer,” they said.

Several such trials are underway to evaluate the role of the pembrolizumab, nivolumab, nivolumab plus ipilimumab, and durvalumab in HIV-infected patients with advanced-stage cancers, according to the review authors.

In the present systematic review, Dr. Cook and Dr. Kim conducted a literature search and reviewed presentations from major annual medical conferences.

Of the 73 HIV-infected patients they identified, most had non–small cell lung cancer (34.2%), melanoma (21.9%), or Kaposi sarcoma (12.3%), while the rest had anal cancer, head and neck cancer, or other malignancies. Most patients had received either nivolumab (39.7%) or pembrolizumab (35.6%).

There were “no concerning findings” among these patients with regard to immune-mediated toxicities or changes in HIV-related parameters.

Six of 70 patients had immune-related adverse events of grade 3 or greater.

Thirty-four patients had documented HIV loads before and after receiving an immune checkpoint inhibitor. Of those, 28 had undetectable HIV loads at baseline, and all but 2 (7%) maintained undetectable loads in the posttreatment evaluation.

Of the remaining six with detectable HIV loads before treatment, five had a decrease in viral load, to the point that four had undetectable HIV viral load in the posttreatment evaluation, the investigators reported.

The overall response rate was 30% for the lung cancer patients, 27% for melanoma, and 63% for Kaposi sarcoma.

In the non–small cell lung cancer subset, response rates were 26% for those who had received previous systemic treatment, and 50% for those who had not, which was similar to findings from major checkpoint inhibitor trials that excluded HIV-infected individuals, the investigators said.

The American Society of Clinical Oncology Conquer Cancer Foundation and Georgetown University supported the study. Dr. Kim reported disclosures related to CARIS Life Science and AstraZeneca.

SOURCE: Cook MR and Kim C. JAMA Oncol. 2019 Feb 7. doi: 10.1001/jamaoncol.2018.6737.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

WASHINGTON – Combination enoblituzumab and pembrolizumab showed acceptable safety and encouraging antitumor activity in select patients with B7-H3-expressing non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), and other solid tumors in a phase 1 dose-escalation and expansion study.

Of note, the combination showed activity in patients anticipated to be poorly responsive to checkpoint inhibitor therapy alone, Charu Aggarwal, MD, of the University of Pennsylvania, Philadelphia, reported at the annual meeting of the Society for Immunotherapy of Cancer.

In all, 133 patients were treated weekly with 3, 10 or 15 mg/kg intravenous doses of the investigational anti-B7-H3 monoclonal antibody enoblituzumab plus 2 mg/kg intravenous doses of the programmed death-1 (PD-1) inhibitor pembrolizumab every 3 weeks (the standard dose at the time) for up to 1 year in the open-label dose-escalation study. Of those, 85% experienced treatment-related adverse events (AEs), and 27.1% experienced grade 3 or higher AEs, Dr. Aggarwal said.

These AEs were mostly infusion-related reactions typically seen with the first dose, and they were not usually cumulative, she said, noting that the rates of immune-related adverse events were less than 5%, about 7% of patients discontinued treatment because of a drug-related AE, and 1 treatment-related death due to pneumonitis occurred.

“No maximum tolerated dose was reached,” she added. “What I want to emphasize is that this is a combination immunotherapy approach, and what we found was that despite a combination approach, the nature, rate, and incidence of immune-related adverse events was not different than what is expected compared to single-agent [therapy] alone.”

Patients were then divided into disease-specific dose-expansion cohorts and the SCCHN and NSCLC cohorts were further stratified based on whether or not they had prior exposure to PD-1 inhibitor therapy.

Antitumor activity was noted in anti-PD-1-naive SCCHN patients, and objective responses were also seen in NSCLC patient with tumor programmed death-ligand 1 (PD-L1) expression of less than 1% and patients with checkpoint inhibitor–refractory urothelial carcinoma.

“We saw a 33.3% response rate in IO [immunotherapy]-naive head and neck cancer patients, and a 35.7% response rate in patients with PD-L1-negative immunotherapy-naive non–small-cell lung cancer patients,” she said.

No objective radiographic responses were seen in the IO-exposed SCCHN patients, but a few were seen in the other tumor cohorts, she noted.

“What was more interesting is this prolonged and high level of stable disease that we found in patients who had been previously treated with IO and had actually experienced significant clinical and radiographic progression then experienced stability with this combination,” she said, noting that “a fair amount of stable disease” was also seen in the IO-naive SCCHN and NSCLC patients.

In the immunotherapy-naive SCCHN patients, responses were seen regardless of human papillomavirus status, and four are still on treatment. One had a confirmed complete response.

“The majority of our patients on our trial and in this cohort were B7-H3-positive, she said, adding that the responses that were seen, including in those with stable disease, were “sustained and durable.”

Responses were similar in the immunotherapy-naive NSCLC patients who were PD-L1 negative, she said.

“Responses were seen irrespective of histology ... and many of these patients are still on treatment,” she added, noting that most were B7-H3-positive, which “seems to select our patients who have an even higher response rate of about 45%.”

The responses in that cohort also occurred early, were durable, and are sustained, and some patients remain on treatment and “are enjoying the clinical benefit afforded by this combination,” she said.

The findings are notable, because B7-H3 is highly expressed in many solid tumors, and monotherapy with enoblituzumab, which targets B7-H3 and is engineered to enhance antibody-dependent cell-mediated cytotoxicity, has demonstrated antitumor activity with an acceptable safety profile in patients with selected solid tumors.

In this study it was combined with pembrolizumab to test the hypothesis that coordinated engagement of both innate and adaptive immunity via the targeting of two distinct members of the B7 family could achieve greater antitumor activity than either agent alone, she explained.

The results “benchmark favorably” versus prior experience with PD-1 agents; pembrolizumab and nivolumab each lead to activity of about 13%-16%, she said.

“We acknowledge that our study has very small numbers. Nevertheless, these are encouraging data ... in this very tough-to-treat population,” Dr. Aggarwal said, adding that “further investigation of enoblituzumab with an anti-PD-1 molecule is warranted in both head and neck and lung cancer patients, perhaps including in combination with chemotherapy.”

Further, given the expression patterns of B7-H3 on a wide variety of solid tumors, further investigation of this combination ... is warranted in other tumor types, including in both checkpoint-naive and -treated populations, she concluded.

This study was sponsored by MacroGenics. Dr. Aggarwal reported receiving consulting fees from BMS.

SOURCE: Aggarwal C et al., SITC 2018 Abstract O24.

Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

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Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

Click here to read the digital edition.

Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

Click here to read the digital edition.

Smoking and exposure to secondhand smoke cost the United States more than $1.9 million over the lifetime of each smoker, according to the personal financial website WalletHub.

Economic and societal losses related to 37.8 million U.S. tobacco users – including out-of-pocket spending for cigarettes, health care expenses, and lost income – top $300 billion annually, but those costs vary considerably by state, WalletHub said in a recent report.

The state with the highest lifetime cost per smoker is Connecticut, with an estimated total of $2.85 million. That works out to just under $56,000 a year for 51 years because lifetime use was defined as one pack a day starting at age 18 years and continuing until age 69 years. New York has the second-highest lifetime cost, which also rounds off to $2.85 million, followed by the District of Columbia ($2.81 million), Massachusetts ($2.76 million), and Rhode Island ($2.68 million), WalletHub said.

Georgia has the lowest lifetime cost of any state – $1.40 million per smoker – followed by Missouri at $1.41 million, North Carolina at $1.42 million, Mississippi at $1.43 million, and South Carolina at $1.44 million, according to the report.

WalletHub’s formula for total lifetime cost has five components: out-of-pocket cost (one pack of cigarettes per day for 51 years), financial opportunity cost (defined as “the amount of return a person would have earned by instead investing that money in the stock market”), health care cost (spending on treatment for smoking-related health complications), income loss (an average 8% decrease caused by absenteeism and lost productivity), and other costs (loss of a homeowner’s insurance credit and costs of secondhand exposure).

The analysis was based on data from the U.S. Census Bureau, Bureau of Labor Statistics, Centers for Disease Control and Prevention, Insurance Information Institute, Campaign for Tobacco-Free Kids, NYsmokefree.com, Federal Reserve Economic Data, Kaiser Family Foundation, and the Independent Insurance Agents & Brokers of America.

rfranki@mdedge.com

Smoking and exposure to secondhand smoke cost the United States more than $1.9 million over the lifetime of each smoker, according to the personal financial website WalletHub.

Economic and societal losses related to 37.8 million U.S. tobacco users – including out-of-pocket spending for cigarettes, health care expenses, and lost income – top $300 billion annually, but those costs vary considerably by state, WalletHub said in a recent report.

The state with the highest lifetime cost per smoker is Connecticut, with an estimated total of $2.85 million. That works out to just under $56,000 a year for 51 years because lifetime use was defined as one pack a day starting at age 18 years and continuing until age 69 years. New York has the second-highest lifetime cost, which also rounds off to $2.85 million, followed by the District of Columbia ($2.81 million), Massachusetts ($2.76 million), and Rhode Island ($2.68 million), WalletHub said.

Georgia has the lowest lifetime cost of any state – $1.40 million per smoker – followed by Missouri at $1.41 million, North Carolina at $1.42 million, Mississippi at $1.43 million, and South Carolina at $1.44 million, according to the report.

WalletHub’s formula for total lifetime cost has five components: out-of-pocket cost (one pack of cigarettes per day for 51 years), financial opportunity cost (defined as “the amount of return a person would have earned by instead investing that money in the stock market”), health care cost (spending on treatment for smoking-related health complications), income loss (an average 8% decrease caused by absenteeism and lost productivity), and other costs (loss of a homeowner’s insurance credit and costs of secondhand exposure).

The analysis was based on data from the U.S. Census Bureau, Bureau of Labor Statistics, Centers for Disease Control and Prevention, Insurance Information Institute, Campaign for Tobacco-Free Kids, NYsmokefree.com, Federal Reserve Economic Data, Kaiser Family Foundation, and the Independent Insurance Agents & Brokers of America.

rfranki@mdedge.com

Smoking and exposure to secondhand smoke cost the United States more than $1.9 million over the lifetime of each smoker, according to the personal financial website WalletHub.

Economic and societal losses related to 37.8 million U.S. tobacco users – including out-of-pocket spending for cigarettes, health care expenses, and lost income – top $300 billion annually, but those costs vary considerably by state, WalletHub said in a recent report.

The state with the highest lifetime cost per smoker is Connecticut, with an estimated total of $2.85 million. That works out to just under $56,000 a year for 51 years because lifetime use was defined as one pack a day starting at age 18 years and continuing until age 69 years. New York has the second-highest lifetime cost, which also rounds off to $2.85 million, followed by the District of Columbia ($2.81 million), Massachusetts ($2.76 million), and Rhode Island ($2.68 million), WalletHub said.

Georgia has the lowest lifetime cost of any state – $1.40 million per smoker – followed by Missouri at $1.41 million, North Carolina at $1.42 million, Mississippi at $1.43 million, and South Carolina at $1.44 million, according to the report.

WalletHub’s formula for total lifetime cost has five components: out-of-pocket cost (one pack of cigarettes per day for 51 years), financial opportunity cost (defined as “the amount of return a person would have earned by instead investing that money in the stock market”), health care cost (spending on treatment for smoking-related health complications), income loss (an average 8% decrease caused by absenteeism and lost productivity), and other costs (loss of a homeowner’s insurance credit and costs of secondhand exposure).

The analysis was based on data from the U.S. Census Bureau, Bureau of Labor Statistics, Centers for Disease Control and Prevention, Insurance Information Institute, Campaign for Tobacco-Free Kids, NYsmokefree.com, Federal Reserve Economic Data, Kaiser Family Foundation, and the Independent Insurance Agents & Brokers of America.

rfranki@mdedge.com

WASHINGTON – The personalized NEO-PV-1 neoantigen vaccine plus poly-ICLC adjuvant in combination with the checkpoint inhibitor nivolumab is well tolerated and shows clinical activity, according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.

No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.

Most adverse events that occurred were mild and related to the local injection, she noted.

Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.

All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.

“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.

The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.

As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.

“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.

Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.

An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.

The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.

“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.

Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.

SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.

WASHINGTON – The personalized NEO-PV-1 neoantigen vaccine plus poly-ICLC adjuvant in combination with the checkpoint inhibitor nivolumab is well tolerated and shows clinical activity, according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.

No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.

Most adverse events that occurred were mild and related to the local injection, she noted.

Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.

All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.

“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.

The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.

As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.

“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.

Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.

An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.

The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.

“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.

Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.

SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.

WASHINGTON – The personalized NEO-PV-1 neoantigen vaccine plus poly-ICLC adjuvant in combination with the checkpoint inhibitor nivolumab is well tolerated and shows clinical activity, according to findings from the ongoing phase 1b NT-001study of patients with metastatic melanoma, smoking-associated non–small cell lung cancer (NSCLC), and bladder cancer.

No vaccine-related serious adverse events occurred in 34 patients in a per-protocol set who were treated with the regimen, Siwen Hu-Lieskovan, MD, PhD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

“We found that NEO-PV-01 in combination with nivolumab was very safe; we did not see any grade 3 to grade 4 toxicity associated with the combination,” said Dr. Hu-Lieskovan, a medical oncologist at the University of California, Los Angeles.

Most adverse events that occurred were mild and related to the local injection, she noted.

Although safety was the primary endpoint of the study, Dr. Hu-Lieskovan and her colleagues also looked at immune responses and treatment efficacy, however, with respect to translational data her presentation addressed only the findings in the melanoma and lung cancer patients.

All patients exhibited an immune response to the vaccine, with 56% of the epitopes generating CD4- and/or CD8-positive T cell responses.

“These immune responses were very durable and still could be detected 52 weeks into the treatment,” she said. Additionally, epitope spreading – increased immune response targeting nonvaccine epitopes (which is indirect evidence of vaccine-induced tumor toxicity) – was observed in 8 of 10 patients tested.

The study subjects, including 16 adults with melanoma, 11 with NSCLC, and 7 with bladder cancer, were treated with nivolumab every 2 weeks for 12 weeks prior to vaccination (while their personalized vaccine was being developed). NEO-PV-01 – which included up to 20 unique peptides plus the immunostimulant poly-ICLC – was then administered subcutaneously in five priming doses followed by two booster doses over the next 12 weeks. Of note, very few patients had programmed cell death protein 1 expression of 50% or greater, including only 13.3%, 28.6%, and 0% of the melanoma, NSCLC, and bladder cancer patients, respectively, and tumor mutation burden was consistent with published reports, she said.

As for efficacy, 11 of 16 melanoma patients (68.6%) had either a partial response (8 pre vaccination and an additional 3 post vaccination) or stable disease. One (6.3%) had a postvaccination complete response, Dr. Hu-Lieskovan said.

“[This is] much better than the historical data,” she noted, adding that 12 patients (75%) are still on the study and continuing treatment with response duration of at least 39.7 weeks.

Of the 11 NSCLC patients, 5 (45.5%) had a partial response (3 pre vaccination and 2 post vaccination), and none had a complete response. Seven (63.6%) remained on the study and were continuing treatment, and response duration was at least 30.6 weeks.

An exploratory analysis of tumor responses after vaccination showed that the majority of melanoma patients and half of the lung cancer patients had further tumor shrinkage after vaccination, and some patients were converted to responders. Most – including some with stable or progressive disease – stayed on treatment, she said.

The findings demonstrate that NEO-PV-01 is very well tolerated and associated with post vaccine responses observed after week 24.

“We saw evidence of vaccination-induced immune response specific to the injected vaccine, as well as epitope spreading, and the T cells induced by these neoantigens can traffic into the tumor and they seem to be functional,” she concluded.

Dr. Hu-Lieskovan reported receiving consulting fees and/or research support from Amgen, BMS, Genmab, Merck, and Vaccinex. She is the UCLA site principal investigator for the NT-001 study and has conducted contracted research for Astellas, F Star, Genentech, Nektar Therapeutics, Neon Therapeutics, Pfizer, Plexxikon, and Xencor.

SOURCE: Hu-Lieskovan S et al. SITC 2018, Abstract 07.

Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.

A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.

The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”

To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).

The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.

Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.

HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.

In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.

Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.

The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.

“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.

The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.

SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.

Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.

A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.

The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”

To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).

The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.

Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.

HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.

In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.

Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.

The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.

“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.

The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.

SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.

Oncologists should consider testing all patients with newly diagnosed cancers for infection with the hepatitis B and C viruses, a multicenter team has recommended.

A prospective study of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infections among 3,051 patients with newly diagnosed cancers showed that 6.5% of patients tested positive for previous HBV and 0.6% had chronic HBV infection. In addition, 2.4% of patients were positive for HCV, and 1.1% for HIV infections, reported Scott D. Ramsey, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

“Many patients had no known risk factors for infection, suggesting that current risk-based models for screening may be insufficient. Thus, we believe our results warrant consideration of universal testing of patients with newly diagnosed cancer for HBV and HCV infection, particularly if such an approach is shown to be cost effective,” they wrote in JAMA Oncology.

The investigators noted that patients with undiagnosed hepatitis and/or HIV infections could transmit them to unsuspecting caregivers, adding that “with effective treatments available, not screening for these viruses misses an opportunity to reduce future morbidity associated with these infections and to avoid viral reactivation during treatment, with resulting morbidity and mortality.”

To estimate the prevalence of the infections in patients with newly diagnosed cancers, investigators looked at a cohort of 3,051 patients with a cancer diagnosis made within the previous 120 days at nine academic medical centers and nine community oncology centers representing a total of 41 cancer clinics affiliated with the SWOG Cancer Research Network (formerly the Southwest Oncology Group).

The median patient age was 60.6 years. Female patients constitute 60.4% of the sample; 18.1% were black, and 18.3% were of Hispanic heritage.

Of 3,050 patients for whom HBV testing results were available, 6.5% (197) were positive for previous HBV infection, compared with an estimated U.S. population prevalence of 4.7%. In addition, 0.6% (19 patients) were found to have chronic HBV, compared with an estimated 0.3% US population prevalence.

HCV infections were detected in 2.4% (71 of 2990 patients), compared with an estimated population prevalence of 1.3%, and HIV infections were detected in 1.1%, compared with a background estimated population prevalence of 0.3%.

In all, 32 patients were diagnosed with viral infections by testing performed for the study, including 8 patients with chronic HBV, 22 with HCV, and 2 with HIV.

Additionally, the authors found that 4 patients with chronic HBV, 23 with HCV, and 7 with HIV had no identifiable risk factors.

The highest prevalence of infections occurred among patients with liver cancer, nonliver and noncolorectal cancers of the gastrointestinal tract, head and neck cancers, lung cancers, and prostate cancer. A finding of viral positivity changed the treatment plan in only 8% of all infected patients, however.

“Given that most HIV-infected patients in our study knew their viral status, the yield of universal HIV testing among patients with newly diagnosed cancer may likely be low. Although age-directed screening is recommended for HIV and HCV, uptake rates in primary care are variable and low overall,” Dr. Ramsey and his colleagues wrote.

The study was supported by grants from the National Cancer Institute. Dr. Ramsey and several co-authors reported receiving NCI grants, and multiple co-authors reported grants and/or consulting fees from various companies.

SOURCE: Ramsey SD et al. JAMA Oncol. 2019 Jan 17. doi: 10.1001/jamaoncol.2018.6437.