Pharmacology

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

The Food and Drug Administration is warning that the entire class of the cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors used to treat advanced breast cancer may cause rare but severe inflammation of the lungs.

“We reviewed CDK 4/6 inhibitors cases from completed and ongoing clinical trials undertaken by manufacturers and their postmarket safety databases that described specific types of inflammation of the lungs, called interstitial lung disease and pneumonitis. Across the entire drug class, there were reports of serious cases, including fatalities,” the FDA said in a press statement.

The overall benefit of CDK 4/6 inhibitors, however, is still greater than the risks when used as prescribed, the agency said.

CDK 4/6 inhibitors are used in combination with hormone therapies to treat adults with hormone receptor–positive, human epidermal growth factor 2–negative advanced or metastatic breast cancer that has spread to other parts of the body. The FDA approved the CDK 4/6 inhibitors palbociclib (Ibrance) in 2015 and ribociclib (Kisqali) and abemaciclib (Verzenio) in 2017, based on improvements in progression-free survival.

Health care professionals should monitor patients regularly for pulmonary symptoms indicative of interstitial lung disease and/or pneumonitis. Signs and symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams in patients in whom infectious, neoplastic, and other causes have been excluded. Interrupt CDK 4/6 inhibitor treatment in patients who have new or worsening respiratory symptoms, and permanently discontinue treatment in patients with severe interstitial lung disease and/or pneumonitis, the FDA said.






 

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Men and women react differently to common drugs used to treat heart failure with reduced ejection fraction (HFrEF), according to findings from a new European study, and women may be able to safely cut their doses in half and get the same level of relief as that provided by larger doses.

“This study ... brings into question what the true optimal medical therapy is for women versus men,” the study authors, led by Bernadet T. Santema, MD, of the University Medical Center Groningen (the Netherlands), wrote in an article published in the Lancet.

Dr. Santema and colleagues noted that current guidelines for the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers for men and women with heart failure do not differentiate between the genders, despite findings showing that, “with the same dose, the maximum plasma concentrations of ACE inhibitors, ARBs, and beta-blockers were up to 2.5 times higher in women than in men.”

In addition, the researchers wrote, women are much more likely than men to suffer side effects from medications, and the effects tend to be more severe.

HFrEF accounts for an estimated 50% of the 5.7 million patients with heart failure in the United States (Nat Rev Dis Primers. 2017 Aug 24. doi: 10.1038/nrdp.2017.58; Card Fail Rev. 2017;3[1]:7-11.)

For the new study, researchers launched an ad hoc analysis of the findings of a prospective study of HFrEF patients in 11 European countries (1,308 men and 402 women) who took drugs in the three classes. Patients were receiving suboptimal medication doses at the start of the study, and physicians were encouraged to increase their medication. The median follow-up for the primary endpoint was 21 months.

“In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and beta-blockers, but women showed about 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels,” the researchers wrote. “These sex differences were still present after adjusting for clinical covariates, including age and body surface area.”

The researchers analyzed an Asian registry (3,539 men, 961 women) as a comparison and found the identical numbers.

“Our study provides evidence supporting the hypothesis that women with HFrEF might have the best outcomes with lower doses of ACE inhibitors or ARBs and beta-blockers than do men, and lower doses than recommended in international guidelines for heart failure,” they wrote. However, they added that it was not likely that sex-specific studies analyzing doses would be performed.

In an accompanying editorial, Heather P. Whitley, PharmD, and Warren D. Smith, PharmD, noted that clinical research has often failed to take gender differences into account. They wrote that the study – the first of its kind – was well executed and raises important questions, but the analysis did not take into account the prevalence of adverse effects or the serum concentrations of the various medications. Although those limitations weaken the findings, the study still offers evidence that gender-based, drug-dose guidelines deserve consideration, wrote Dr. Whitley, of Auburn (Ala.) University, and Dr. Smith, of Baptist Health System, Montgomery, Ala (Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736[19]31812-4).

The study was funded by the European Commission. Several study authors reported various disclosures. Dr. Whitley and Dr. Smith reported no conflicts of interest.

SOURCE: Santema BT et al. Lancet. 2019 Aug 22. doi: 10.1016/S0140-6736(19)31792-1.

Administering an HIV drug concurrently with chemoradiotherapy resulted in promising local control and overall survival in patients with unresectable, locally advanced non–small cell lung cancer, researchers reported.

There was no overt exacerbation of the toxic effects of chemoradiotherapy with the addition of nelfinavir, a protease inhibitor, in the prospective, open-label, phase 1/2 study, the researchers wrote.

Nelfinavir plus chemoradiotherapy yielded a median progression-free survival of 11.7 months and median survival of 41.1 months, while the cumulative local failure incidence was 39% according to their report.

Those outcomes compare favorably with historical data, the investigators wrote in JAMA Oncology.

In benchmark results of the RTOG 0617 study of chemoradiotherapy in locally advanced non–small cell lung cancer, median overall survival was 28.7 months receiving radiotherapy at a standard dose of 60 Gy, and 20.3 months for those receiving high-dose (74 Gy) radiotherapy.

However, a randomized, phase 3 trial is needed to confirm these latest results with a protease inhibitor added to chemotherapy, according to Ramesh Rengan, MD, PhD, of the University of Washington, Seattle, and coinvestigators.

“As nelfinavir is a U.S. Food and Drug Administration–approved oral drug, this treatment approach is feasible and is potentially a readily exportable platform for daily clinical use,” Dr. Rengan and coauthors wrote.

In vitro and in vivo studies have shown that nelfinavir inhibited PI3K and Akt signaling, sensitized tumor cells to ionizing radiation, and improved tumor perfusion in animal models. “We hypothesize that it is these properties that drive the clinical results observed in this study,” Dr. Rengan and coauthors wrote.

They reported on a total of 35 patients with stage IIIA/IIIB non–small cell lung cancer who received nelfinavir at either 625 mg or 1,250 mg twice daily, starting 7-14 days before starting radiotherapy to 66.6 Gy at 1.8 Gy per fraction, and throughout the full course of radiotherapy.

There were no dose-limiting toxic effects observed in the study, and toxic effects were “acceptable,” with no grade 4 nonhematologic toxic effects seen, according to investigators. Leukopenia was the primary grade 3-4 hematologic toxic effect, observed in 2 of 5 patients receiving the lower nelfinavir dose and 18 of 30 at the higher dose.

Beyond non–small cell lung cancer, the efficacy and safety nelfinavir given concurrently with radiotherapy has been looked at in other disease settings. Data from those trials suggest that this protease inhibitor could “augment tumor response” not only in non–small cell lung cancer, but in locally advanced pancreatic cancer and glioblastoma, all of which are relatively radioresistant, according to Dr. Rengan and colleagues.

Study support came from grants from the National Institutes of Health and Abramson Cancer Center, and an American Society for Radiation Oncology training award to Dr. Rengan. Study authors reported disclosures related to Pfizer, 511 Pharma, Progenics Pharmaceuticals, Siemens, Actinium, AstraZeneca, Merck, Bristol-Myers Squibb, and others.

SOURCE: Rengan R et al. JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.2095.

Administering an HIV drug concurrently with chemoradiotherapy resulted in promising local control and overall survival in patients with unresectable, locally advanced non–small cell lung cancer, researchers reported.

There was no overt exacerbation of the toxic effects of chemoradiotherapy with the addition of nelfinavir, a protease inhibitor, in the prospective, open-label, phase 1/2 study, the researchers wrote.

Nelfinavir plus chemoradiotherapy yielded a median progression-free survival of 11.7 months and median survival of 41.1 months, while the cumulative local failure incidence was 39% according to their report.

Those outcomes compare favorably with historical data, the investigators wrote in JAMA Oncology.

In benchmark results of the RTOG 0617 study of chemoradiotherapy in locally advanced non–small cell lung cancer, median overall survival was 28.7 months receiving radiotherapy at a standard dose of 60 Gy, and 20.3 months for those receiving high-dose (74 Gy) radiotherapy.

However, a randomized, phase 3 trial is needed to confirm these latest results with a protease inhibitor added to chemotherapy, according to Ramesh Rengan, MD, PhD, of the University of Washington, Seattle, and coinvestigators.

“As nelfinavir is a U.S. Food and Drug Administration–approved oral drug, this treatment approach is feasible and is potentially a readily exportable platform for daily clinical use,” Dr. Rengan and coauthors wrote.

In vitro and in vivo studies have shown that nelfinavir inhibited PI3K and Akt signaling, sensitized tumor cells to ionizing radiation, and improved tumor perfusion in animal models. “We hypothesize that it is these properties that drive the clinical results observed in this study,” Dr. Rengan and coauthors wrote.

They reported on a total of 35 patients with stage IIIA/IIIB non–small cell lung cancer who received nelfinavir at either 625 mg or 1,250 mg twice daily, starting 7-14 days before starting radiotherapy to 66.6 Gy at 1.8 Gy per fraction, and throughout the full course of radiotherapy.

There were no dose-limiting toxic effects observed in the study, and toxic effects were “acceptable,” with no grade 4 nonhematologic toxic effects seen, according to investigators. Leukopenia was the primary grade 3-4 hematologic toxic effect, observed in 2 of 5 patients receiving the lower nelfinavir dose and 18 of 30 at the higher dose.

Beyond non–small cell lung cancer, the efficacy and safety nelfinavir given concurrently with radiotherapy has been looked at in other disease settings. Data from those trials suggest that this protease inhibitor could “augment tumor response” not only in non–small cell lung cancer, but in locally advanced pancreatic cancer and glioblastoma, all of which are relatively radioresistant, according to Dr. Rengan and colleagues.

Study support came from grants from the National Institutes of Health and Abramson Cancer Center, and an American Society for Radiation Oncology training award to Dr. Rengan. Study authors reported disclosures related to Pfizer, 511 Pharma, Progenics Pharmaceuticals, Siemens, Actinium, AstraZeneca, Merck, Bristol-Myers Squibb, and others.

SOURCE: Rengan R et al. JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.2095.

Administering an HIV drug concurrently with chemoradiotherapy resulted in promising local control and overall survival in patients with unresectable, locally advanced non–small cell lung cancer, researchers reported.

There was no overt exacerbation of the toxic effects of chemoradiotherapy with the addition of nelfinavir, a protease inhibitor, in the prospective, open-label, phase 1/2 study, the researchers wrote.

Nelfinavir plus chemoradiotherapy yielded a median progression-free survival of 11.7 months and median survival of 41.1 months, while the cumulative local failure incidence was 39% according to their report.

Those outcomes compare favorably with historical data, the investigators wrote in JAMA Oncology.

In benchmark results of the RTOG 0617 study of chemoradiotherapy in locally advanced non–small cell lung cancer, median overall survival was 28.7 months receiving radiotherapy at a standard dose of 60 Gy, and 20.3 months for those receiving high-dose (74 Gy) radiotherapy.

However, a randomized, phase 3 trial is needed to confirm these latest results with a protease inhibitor added to chemotherapy, according to Ramesh Rengan, MD, PhD, of the University of Washington, Seattle, and coinvestigators.

“As nelfinavir is a U.S. Food and Drug Administration–approved oral drug, this treatment approach is feasible and is potentially a readily exportable platform for daily clinical use,” Dr. Rengan and coauthors wrote.

In vitro and in vivo studies have shown that nelfinavir inhibited PI3K and Akt signaling, sensitized tumor cells to ionizing radiation, and improved tumor perfusion in animal models. “We hypothesize that it is these properties that drive the clinical results observed in this study,” Dr. Rengan and coauthors wrote.

They reported on a total of 35 patients with stage IIIA/IIIB non–small cell lung cancer who received nelfinavir at either 625 mg or 1,250 mg twice daily, starting 7-14 days before starting radiotherapy to 66.6 Gy at 1.8 Gy per fraction, and throughout the full course of radiotherapy.

There were no dose-limiting toxic effects observed in the study, and toxic effects were “acceptable,” with no grade 4 nonhematologic toxic effects seen, according to investigators. Leukopenia was the primary grade 3-4 hematologic toxic effect, observed in 2 of 5 patients receiving the lower nelfinavir dose and 18 of 30 at the higher dose.

Beyond non–small cell lung cancer, the efficacy and safety nelfinavir given concurrently with radiotherapy has been looked at in other disease settings. Data from those trials suggest that this protease inhibitor could “augment tumor response” not only in non–small cell lung cancer, but in locally advanced pancreatic cancer and glioblastoma, all of which are relatively radioresistant, according to Dr. Rengan and colleagues.

Study support came from grants from the National Institutes of Health and Abramson Cancer Center, and an American Society for Radiation Oncology training award to Dr. Rengan. Study authors reported disclosures related to Pfizer, 511 Pharma, Progenics Pharmaceuticals, Siemens, Actinium, AstraZeneca, Merck, Bristol-Myers Squibb, and others.

SOURCE: Rengan R et al. JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.2095.

Zoledronic acid was effective at preventing symptomatic periodontal disease in patients with osteoporosis and good oral hygiene, according to Akira Taguchi, DDS, PhD, of the department of oral and maxillofacial radiology at Matsumoto Dental University, Nagano, Japan, and associates.

bernardbodo/iStock/Getty Images Plus

In a study published in Menopause, the investigators retrospectively analyzed 542 men and women with osteoporosis who participated in the randomized ZONE (Zoledronate Treatment in Efficacy to Osteoporosis) trial. Patients received either zoledronic acid (n = 258) or placebo (n = 284) once yearly for 2 years by IV infusion; mean age was 74 years in both groups. Patients were instructed to maintain good oral health at baseline and every 3 months afterward. Participants with signs or symptoms involving the oral cavity at the follow-up approximately every 3 months were referred to dentists for examination of oral disease.

Oral adverse events were significantly more common in the placebo group, compared with the zoledronic acid group (20% vs. 14%; P = .04); incidence of symptomatic periodontal disease also was significantly more common in those receiving placebo (12% vs. 5%; P = .002). While loss of teeth was more common in the control group than in those receiving zoledronic acid (11% vs. 7%), the difference was not significant.

“Because zoledronic acid can prevent symptomatic periodontal disease when combined with good oral hygiene management, it is possible that the procedures performed in this study could eventually suppress the development of [osteonecrosis of the jaw],” the investigators concluded.

The study was funded by Asahi-Kasei Pharma. The investigators reported employment or receiving consulting fees from numerous pharmaceutical companies.

[email protected]

SOURCE: Taguchi A et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001393.

Zoledronic acid was effective at preventing symptomatic periodontal disease in patients with osteoporosis and good oral hygiene, according to Akira Taguchi, DDS, PhD, of the department of oral and maxillofacial radiology at Matsumoto Dental University, Nagano, Japan, and associates.

bernardbodo/iStock/Getty Images Plus

In a study published in Menopause, the investigators retrospectively analyzed 542 men and women with osteoporosis who participated in the randomized ZONE (Zoledronate Treatment in Efficacy to Osteoporosis) trial. Patients received either zoledronic acid (n = 258) or placebo (n = 284) once yearly for 2 years by IV infusion; mean age was 74 years in both groups. Patients were instructed to maintain good oral health at baseline and every 3 months afterward. Participants with signs or symptoms involving the oral cavity at the follow-up approximately every 3 months were referred to dentists for examination of oral disease.

Oral adverse events were significantly more common in the placebo group, compared with the zoledronic acid group (20% vs. 14%; P = .04); incidence of symptomatic periodontal disease also was significantly more common in those receiving placebo (12% vs. 5%; P = .002). While loss of teeth was more common in the control group than in those receiving zoledronic acid (11% vs. 7%), the difference was not significant.

“Because zoledronic acid can prevent symptomatic periodontal disease when combined with good oral hygiene management, it is possible that the procedures performed in this study could eventually suppress the development of [osteonecrosis of the jaw],” the investigators concluded.

The study was funded by Asahi-Kasei Pharma. The investigators reported employment or receiving consulting fees from numerous pharmaceutical companies.

[email protected]

SOURCE: Taguchi A et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001393.

Zoledronic acid was effective at preventing symptomatic periodontal disease in patients with osteoporosis and good oral hygiene, according to Akira Taguchi, DDS, PhD, of the department of oral and maxillofacial radiology at Matsumoto Dental University, Nagano, Japan, and associates.

bernardbodo/iStock/Getty Images Plus

In a study published in Menopause, the investigators retrospectively analyzed 542 men and women with osteoporosis who participated in the randomized ZONE (Zoledronate Treatment in Efficacy to Osteoporosis) trial. Patients received either zoledronic acid (n = 258) or placebo (n = 284) once yearly for 2 years by IV infusion; mean age was 74 years in both groups. Patients were instructed to maintain good oral health at baseline and every 3 months afterward. Participants with signs or symptoms involving the oral cavity at the follow-up approximately every 3 months were referred to dentists for examination of oral disease.

Oral adverse events were significantly more common in the placebo group, compared with the zoledronic acid group (20% vs. 14%; P = .04); incidence of symptomatic periodontal disease also was significantly more common in those receiving placebo (12% vs. 5%; P = .002). While loss of teeth was more common in the control group than in those receiving zoledronic acid (11% vs. 7%), the difference was not significant.

“Because zoledronic acid can prevent symptomatic periodontal disease when combined with good oral hygiene management, it is possible that the procedures performed in this study could eventually suppress the development of [osteonecrosis of the jaw],” the investigators concluded.

The study was funded by Asahi-Kasei Pharma. The investigators reported employment or receiving consulting fees from numerous pharmaceutical companies.

[email protected]

SOURCE: Taguchi A et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001393.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.

Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”

“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.

“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”

Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).

“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.

Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”

SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

The Food and Drug Administration has announced its approval of lefamulin (Xenleta) for the treatment of community-acquired bacterial pneumonia in adults.

Olivier Le Moal/Getty Images

Approval was based on results of two clinical trials assessing a total of 1,289 people with community-acquired bacterial pneumonia. In these trials, lefamulin was compared with moxifloxacin with and without linezolid. Patients who received lefamulin had similar rates of treatment success as those taking moxifloxacin alone or moxifloxacin plus linezolid.

The most common adverse reactions associated with lefamulin include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. Patients with prolonged QT interval, patients with arrhythmias, patients receiving treatment with antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval are contraindicated. In addition, because of evidence of fetal harm in animal studies, pregnant women should be advised of potential risks before receiving lefamulin.

“This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease. For managing this serious disease, it is important for physicians and patients to have treatment options,” Ed Cox, MD, MPH, director of the FDA’s Office of Antimicrobial Products, said in the press release.

[email protected]

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

The direct oral anticoagulants (DOACs) apixaban and rivaroxaban are now among the options for thromboprophylaxis in high-risk cancer outpatients with low risk for bleeding and drug interactions, according to a practice guideline update from the American Society of Clinical Oncology.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban also has been added as an option for initial anticoagulation for venous thromboembolism (VTE), and both rivaroxaban and edoxaban are now options for long-term anticoagulation, Nigel S. Key, MB ChB, and colleagues wrote in the updated guideline on the prophylaxis and treatment of VTE – including deep vein thrombosis (DVT) and pulmonary embolism (PE) – in cancer patients (J Clin Oncol. 2019 Aug 5. doi: 10.1200/JCO.19.19.01461).

The addition of DOACs as options for VTE prophylaxis and treatment represents the most notable change to the guideline.

“Oral anticoagulants that target thrombin (direct thrombin inhibitor, dabigatran) or activated factor X (antifactor Xa inhibitors, rivaroxaban, apixaban, and edoxaban) are now approved for treatment of DVT or PE as well as for DVT prophylaxis following orthopedic surgery and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation,” the guideline panel wrote.

A systematic review of PubMed and the Cochrane Library for randomized controlled trials (RCTs) and meta-analyses of RCTs published from Aug. 1, 2014, through Dec. 4, 2018, identified 35 publications on VTE prophylaxis and treatment, including 2 RCTs of DOACs for prophylaxis and 2 others of DOAC treatment, as well as 8 publications on VTE risk assessment. A multidisciplinary expert panel appointed by ASCO and cochaired by Dr. Key of the University of North Carolina, Chapel Hill, used this evidence to develop the updated guideline.

The work was guided by “the ‘signals’ approach that is designed to identify only new, potentially practice-changing data – signals – that might translate into revised practice recommendations,” the authors explained.

DOAC-related updates

VTE prophylaxis. Based in part on findings from the recently published AVERT trial of apixaban in patients initiating a new course of chemotherapy and from the CASSINI trial of rivaroxaban in patients with solid tumors or lymphoma starting systemic antineoplastic therapy, the panel added both agents as thromboprophylactic options that can be offered to high-risk cancer outpatients with no significant risk factors for bleeding or drug interactions (N Engl J Med. 2019;380:711-19; N Engl J Med. 2019;380:720-8).

Low-molecular-weight heparin (LMWH) also remains an option in such patients; consideration of therapy should involve discussion with the patient about relative benefits and harms, drug costs, and “the uncertainty surrounding duration of prophylaxis in this setting,” they wrote.

Anticoagulation for VTE. Options for initial anticoagulation include LMWH, unfractionated heparin (UFH), fondaparinux, and now rivaroxaban, with the latter added based on findings from two RCTs – the SELECT-D trial and the Hokusai VTE-Cancer study – and multiple meta-analyses (J Clin Oncol. 2018;36:2017-23; N Engl J Med. 2018;378:615-24).

Long-term anticoagulation can involve treatment with LMWH, edoxaban, or rivaroxaban for at least 6 months, all of which have improved efficacy versus vitamin K agonists (VKAs), the panel noted. However, VKAs may be used if LMWH and DOACs are not accessible.

Importantly, the literature indicates an increased risk of major bleeding with DOACs, particularly in patients with gastrointestinal malignancies and potentially in those with genitourinary malignancies. “Caution with DOACs is also warranted in other settings with high risk for mucosal bleeding,” the panel wrote.
 

Additional updates

CNS metastases. The anticoagulation recommendations were also updated to include patients with metastatic central nervous system malignancies (those with primary CNS malignancies were included previously). Both those with primary and metastatic CNS malignancy should be offered anticoagulation for established VTE as described for patients with other types of cancer. However, the panel stressed that “uncertainties remain about choice of agents and selection of patients most likely to benefit.”

“Patients with intracranial tumors are at increased risk for thrombotic complications and intracranial hemorrhage (ICH), but the presence of a stable or active primary intracranial malignancy or brain metastases is not an absolute contraindication to anticoagulation,” they wrote.

Limited evidence suggests that therapeutic anticoagulation does not increase ICH risk in patients with brain metastases, but it may increase risk in those with primary brain tumors, the panel added.

Additionally, preliminary data from a retrospective cohort of patients with metastatic brain disease and venous thrombosis suggest that DOACs may be associated with a lower risk of ICH than is LMWH in this population.

Long-term postoperative LMWH. Extended prophylaxis with LMWH for up to 4 weeks is recommended after major open or laparoscopic abdominal or pelvic surgery in cancer patients with high-risk features, such as restricted mobility, obesity, history of VTE, or with additional risk factors. Lower-risk surgical settings require case-by-case decision making about appropriate thromboprophylaxis duration, according to the update.

A 2014 RCT looking at thromboprophylaxis duration in 225 patients undergoing laparoscopic surgery for colorectal cancer prompted the addition of laparoscopic surgery to this recommendation. In that study, VTE occurred by 4 weeks in nearly 10% of patients receiving 1 week of prophylaxis and in no patients in the 4-week arm. Major bleeding occurred in one versus zero patients in the thromboprophylaxis arms, respectively (Ann Surg. April 2014;259[4]:665-9).
 

Reaffirmed recommendations

Based on the latest available data, the panel reaffirmed that most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis for the duration of their hospitalization and that thromboprophylaxis should not be routinely recommended for all outpatients with cancer.

The panel also reaffirmed the need for thromboprophylaxis starting preoperatively and continuing for at least 7-10 days in patients undergoing major cancer surgery, the need for periodic assessment of VTE risk in cancer patients, and the importance of patient education about the signs and symptoms of VTE.
 

Perspective and future directions

In an interview, David H. Henry, MD, said he was pleased to see ASCO incorporate the latest DOAC data into the VTE guideline.

The AVERT and CASSINI studies, in particular, highlight the value of using the Khorana Risk Score, which considers cancer type, blood counts, and body mass index to predict the risk of thrombosis in cancer patients and to guide decisions regarding prophylaxis, said Dr. Henry, vice chair of the department of medicine and clinical professor of medicine at Penn Medicine’s Abramson Cancer Center, Philadelphia.

The DOACs also represent “a nice new development in the treatment setting,” he said, adding that it’s been long known – since the 2003 CLOT trial – that cancer patients with VTE had much lower recurrence rates with LMWH versus warfarin (Coumadin).

“Now fast forward to the modern era ... and DOACs now appear to be a good idea,” he said.

Dr. Henry also addressed the recommendation for expanded postoperative LMWH use.

“That I found interesting; I’m not sure what took them so long,” he said, explaining that National Comprehensive Cancer Network and European Society of Medical Oncology recommendations have long stated that, for patients with abdominal cancers who undergo abdominopelvic surgery, DVT prophylaxis should continue for 4 weeks.

Dr. Henry said that a survey at his center showed that those recommendations were “very poorly followed,” with surgeons giving 4 weeks of prophylaxis in just 5% of cases.

“The good news from our survey was that not many people had a VTE, despite not many people following the recommendations, but I must say I think our surgeons are catching on,” he said.

Overall, the updated guideline highlights the importance of considering the “cancer variable” when it comes to VTE prevention and treatment.

“We’ve known forever that when we diagnose a DVT or PE in the outpatient setting – and this is independent of cancer – that you should treat it. Add the cancer variable and we now know that we should worry and try to prevent the VTE in certain high-risk patients, and there are some drugs to do it with,” he said, adding that “you should worry about the person you’ve just provoked [with surgery] as well.”

An important question not addressed in the guideline update is the indefinite use of DOACs in cancer patients with ongoing risk, he said.

“When we see DVT or PE, we usually treat for 3 months – that’s the industry standard – and at the end of 3 months ... you do a time out and you say to yourself, ‘Was this person provoked?’ ” he said.

For example, if they took a long flight or if pregnancy was a factor, treatment can usually be safely stopped. However, in a cancer patient who still has cancer, the provocation continues, and the patient may require indefinite treatment.

Questions that remain involve defining “indefinite” and include whether (and which of) these drugs can be used indefinitely in such patients, Dr. Henry said.

Dr. Key reported receiving honoraria from Novo Nordisk, research funding to his institution from Baxter Biosciences, Grifols, and Pfizer, and serving as a consultant or advisor for Genentech, Roche, Uniqure, Seattle Genetics, and Shire Human Genetic Therapies. Numerous disclosures were also reported by other expert panel members.

[email protected]

The direct oral anticoagulants (DOACs) apixaban and rivaroxaban are now among the options for thromboprophylaxis in high-risk cancer outpatients with low risk for bleeding and drug interactions, according to a practice guideline update from the American Society of Clinical Oncology.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban also has been added as an option for initial anticoagulation for venous thromboembolism (VTE), and both rivaroxaban and edoxaban are now options for long-term anticoagulation, Nigel S. Key, MB ChB, and colleagues wrote in the updated guideline on the prophylaxis and treatment of VTE – including deep vein thrombosis (DVT) and pulmonary embolism (PE) – in cancer patients (J Clin Oncol. 2019 Aug 5. doi: 10.1200/JCO.19.19.01461).

The addition of DOACs as options for VTE prophylaxis and treatment represents the most notable change to the guideline.

“Oral anticoagulants that target thrombin (direct thrombin inhibitor, dabigatran) or activated factor X (antifactor Xa inhibitors, rivaroxaban, apixaban, and edoxaban) are now approved for treatment of DVT or PE as well as for DVT prophylaxis following orthopedic surgery and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation,” the guideline panel wrote.

A systematic review of PubMed and the Cochrane Library for randomized controlled trials (RCTs) and meta-analyses of RCTs published from Aug. 1, 2014, through Dec. 4, 2018, identified 35 publications on VTE prophylaxis and treatment, including 2 RCTs of DOACs for prophylaxis and 2 others of DOAC treatment, as well as 8 publications on VTE risk assessment. A multidisciplinary expert panel appointed by ASCO and cochaired by Dr. Key of the University of North Carolina, Chapel Hill, used this evidence to develop the updated guideline.

The work was guided by “the ‘signals’ approach that is designed to identify only new, potentially practice-changing data – signals – that might translate into revised practice recommendations,” the authors explained.

DOAC-related updates

VTE prophylaxis. Based in part on findings from the recently published AVERT trial of apixaban in patients initiating a new course of chemotherapy and from the CASSINI trial of rivaroxaban in patients with solid tumors or lymphoma starting systemic antineoplastic therapy, the panel added both agents as thromboprophylactic options that can be offered to high-risk cancer outpatients with no significant risk factors for bleeding or drug interactions (N Engl J Med. 2019;380:711-19; N Engl J Med. 2019;380:720-8).

Low-molecular-weight heparin (LMWH) also remains an option in such patients; consideration of therapy should involve discussion with the patient about relative benefits and harms, drug costs, and “the uncertainty surrounding duration of prophylaxis in this setting,” they wrote.

Anticoagulation for VTE. Options for initial anticoagulation include LMWH, unfractionated heparin (UFH), fondaparinux, and now rivaroxaban, with the latter added based on findings from two RCTs – the SELECT-D trial and the Hokusai VTE-Cancer study – and multiple meta-analyses (J Clin Oncol. 2018;36:2017-23; N Engl J Med. 2018;378:615-24).

Long-term anticoagulation can involve treatment with LMWH, edoxaban, or rivaroxaban for at least 6 months, all of which have improved efficacy versus vitamin K agonists (VKAs), the panel noted. However, VKAs may be used if LMWH and DOACs are not accessible.

Importantly, the literature indicates an increased risk of major bleeding with DOACs, particularly in patients with gastrointestinal malignancies and potentially in those with genitourinary malignancies. “Caution with DOACs is also warranted in other settings with high risk for mucosal bleeding,” the panel wrote.
 

Additional updates

CNS metastases. The anticoagulation recommendations were also updated to include patients with metastatic central nervous system malignancies (those with primary CNS malignancies were included previously). Both those with primary and metastatic CNS malignancy should be offered anticoagulation for established VTE as described for patients with other types of cancer. However, the panel stressed that “uncertainties remain about choice of agents and selection of patients most likely to benefit.”

“Patients with intracranial tumors are at increased risk for thrombotic complications and intracranial hemorrhage (ICH), but the presence of a stable or active primary intracranial malignancy or brain metastases is not an absolute contraindication to anticoagulation,” they wrote.

Limited evidence suggests that therapeutic anticoagulation does not increase ICH risk in patients with brain metastases, but it may increase risk in those with primary brain tumors, the panel added.

Additionally, preliminary data from a retrospective cohort of patients with metastatic brain disease and venous thrombosis suggest that DOACs may be associated with a lower risk of ICH than is LMWH in this population.

Long-term postoperative LMWH. Extended prophylaxis with LMWH for up to 4 weeks is recommended after major open or laparoscopic abdominal or pelvic surgery in cancer patients with high-risk features, such as restricted mobility, obesity, history of VTE, or with additional risk factors. Lower-risk surgical settings require case-by-case decision making about appropriate thromboprophylaxis duration, according to the update.

A 2014 RCT looking at thromboprophylaxis duration in 225 patients undergoing laparoscopic surgery for colorectal cancer prompted the addition of laparoscopic surgery to this recommendation. In that study, VTE occurred by 4 weeks in nearly 10% of patients receiving 1 week of prophylaxis and in no patients in the 4-week arm. Major bleeding occurred in one versus zero patients in the thromboprophylaxis arms, respectively (Ann Surg. April 2014;259[4]:665-9).
 

Reaffirmed recommendations

Based on the latest available data, the panel reaffirmed that most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis for the duration of their hospitalization and that thromboprophylaxis should not be routinely recommended for all outpatients with cancer.

The panel also reaffirmed the need for thromboprophylaxis starting preoperatively and continuing for at least 7-10 days in patients undergoing major cancer surgery, the need for periodic assessment of VTE risk in cancer patients, and the importance of patient education about the signs and symptoms of VTE.
 

Perspective and future directions

In an interview, David H. Henry, MD, said he was pleased to see ASCO incorporate the latest DOAC data into the VTE guideline.

The AVERT and CASSINI studies, in particular, highlight the value of using the Khorana Risk Score, which considers cancer type, blood counts, and body mass index to predict the risk of thrombosis in cancer patients and to guide decisions regarding prophylaxis, said Dr. Henry, vice chair of the department of medicine and clinical professor of medicine at Penn Medicine’s Abramson Cancer Center, Philadelphia.

The DOACs also represent “a nice new development in the treatment setting,” he said, adding that it’s been long known – since the 2003 CLOT trial – that cancer patients with VTE had much lower recurrence rates with LMWH versus warfarin (Coumadin).

“Now fast forward to the modern era ... and DOACs now appear to be a good idea,” he said.

Dr. Henry also addressed the recommendation for expanded postoperative LMWH use.

“That I found interesting; I’m not sure what took them so long,” he said, explaining that National Comprehensive Cancer Network and European Society of Medical Oncology recommendations have long stated that, for patients with abdominal cancers who undergo abdominopelvic surgery, DVT prophylaxis should continue for 4 weeks.

Dr. Henry said that a survey at his center showed that those recommendations were “very poorly followed,” with surgeons giving 4 weeks of prophylaxis in just 5% of cases.

“The good news from our survey was that not many people had a VTE, despite not many people following the recommendations, but I must say I think our surgeons are catching on,” he said.

Overall, the updated guideline highlights the importance of considering the “cancer variable” when it comes to VTE prevention and treatment.

“We’ve known forever that when we diagnose a DVT or PE in the outpatient setting – and this is independent of cancer – that you should treat it. Add the cancer variable and we now know that we should worry and try to prevent the VTE in certain high-risk patients, and there are some drugs to do it with,” he said, adding that “you should worry about the person you’ve just provoked [with surgery] as well.”

An important question not addressed in the guideline update is the indefinite use of DOACs in cancer patients with ongoing risk, he said.

“When we see DVT or PE, we usually treat for 3 months – that’s the industry standard – and at the end of 3 months ... you do a time out and you say to yourself, ‘Was this person provoked?’ ” he said.

For example, if they took a long flight or if pregnancy was a factor, treatment can usually be safely stopped. However, in a cancer patient who still has cancer, the provocation continues, and the patient may require indefinite treatment.

Questions that remain involve defining “indefinite” and include whether (and which of) these drugs can be used indefinitely in such patients, Dr. Henry said.

Dr. Key reported receiving honoraria from Novo Nordisk, research funding to his institution from Baxter Biosciences, Grifols, and Pfizer, and serving as a consultant or advisor for Genentech, Roche, Uniqure, Seattle Genetics, and Shire Human Genetic Therapies. Numerous disclosures were also reported by other expert panel members.

[email protected]

The direct oral anticoagulants (DOACs) apixaban and rivaroxaban are now among the options for thromboprophylaxis in high-risk cancer outpatients with low risk for bleeding and drug interactions, according to a practice guideline update from the American Society of Clinical Oncology.

Sebastian Kaulitzki/Thinkstock

Rivaroxaban also has been added as an option for initial anticoagulation for venous thromboembolism (VTE), and both rivaroxaban and edoxaban are now options for long-term anticoagulation, Nigel S. Key, MB ChB, and colleagues wrote in the updated guideline on the prophylaxis and treatment of VTE – including deep vein thrombosis (DVT) and pulmonary embolism (PE) – in cancer patients (J Clin Oncol. 2019 Aug 5. doi: 10.1200/JCO.19.19.01461).

The addition of DOACs as options for VTE prophylaxis and treatment represents the most notable change to the guideline.

“Oral anticoagulants that target thrombin (direct thrombin inhibitor, dabigatran) or activated factor X (antifactor Xa inhibitors, rivaroxaban, apixaban, and edoxaban) are now approved for treatment of DVT or PE as well as for DVT prophylaxis following orthopedic surgery and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation,” the guideline panel wrote.

A systematic review of PubMed and the Cochrane Library for randomized controlled trials (RCTs) and meta-analyses of RCTs published from Aug. 1, 2014, through Dec. 4, 2018, identified 35 publications on VTE prophylaxis and treatment, including 2 RCTs of DOACs for prophylaxis and 2 others of DOAC treatment, as well as 8 publications on VTE risk assessment. A multidisciplinary expert panel appointed by ASCO and cochaired by Dr. Key of the University of North Carolina, Chapel Hill, used this evidence to develop the updated guideline.

The work was guided by “the ‘signals’ approach that is designed to identify only new, potentially practice-changing data – signals – that might translate into revised practice recommendations,” the authors explained.

DOAC-related updates

VTE prophylaxis. Based in part on findings from the recently published AVERT trial of apixaban in patients initiating a new course of chemotherapy and from the CASSINI trial of rivaroxaban in patients with solid tumors or lymphoma starting systemic antineoplastic therapy, the panel added both agents as thromboprophylactic options that can be offered to high-risk cancer outpatients with no significant risk factors for bleeding or drug interactions (N Engl J Med. 2019;380:711-19; N Engl J Med. 2019;380:720-8).

Low-molecular-weight heparin (LMWH) also remains an option in such patients; consideration of therapy should involve discussion with the patient about relative benefits and harms, drug costs, and “the uncertainty surrounding duration of prophylaxis in this setting,” they wrote.

Anticoagulation for VTE. Options for initial anticoagulation include LMWH, unfractionated heparin (UFH), fondaparinux, and now rivaroxaban, with the latter added based on findings from two RCTs – the SELECT-D trial and the Hokusai VTE-Cancer study – and multiple meta-analyses (J Clin Oncol. 2018;36:2017-23; N Engl J Med. 2018;378:615-24).

Long-term anticoagulation can involve treatment with LMWH, edoxaban, or rivaroxaban for at least 6 months, all of which have improved efficacy versus vitamin K agonists (VKAs), the panel noted. However, VKAs may be used if LMWH and DOACs are not accessible.

Importantly, the literature indicates an increased risk of major bleeding with DOACs, particularly in patients with gastrointestinal malignancies and potentially in those with genitourinary malignancies. “Caution with DOACs is also warranted in other settings with high risk for mucosal bleeding,” the panel wrote.
 

Additional updates

CNS metastases. The anticoagulation recommendations were also updated to include patients with metastatic central nervous system malignancies (those with primary CNS malignancies were included previously). Both those with primary and metastatic CNS malignancy should be offered anticoagulation for established VTE as described for patients with other types of cancer. However, the panel stressed that “uncertainties remain about choice of agents and selection of patients most likely to benefit.”

“Patients with intracranial tumors are at increased risk for thrombotic complications and intracranial hemorrhage (ICH), but the presence of a stable or active primary intracranial malignancy or brain metastases is not an absolute contraindication to anticoagulation,” they wrote.

Limited evidence suggests that therapeutic anticoagulation does not increase ICH risk in patients with brain metastases, but it may increase risk in those with primary brain tumors, the panel added.

Additionally, preliminary data from a retrospective cohort of patients with metastatic brain disease and venous thrombosis suggest that DOACs may be associated with a lower risk of ICH than is LMWH in this population.

Long-term postoperative LMWH. Extended prophylaxis with LMWH for up to 4 weeks is recommended after major open or laparoscopic abdominal or pelvic surgery in cancer patients with high-risk features, such as restricted mobility, obesity, history of VTE, or with additional risk factors. Lower-risk surgical settings require case-by-case decision making about appropriate thromboprophylaxis duration, according to the update.

A 2014 RCT looking at thromboprophylaxis duration in 225 patients undergoing laparoscopic surgery for colorectal cancer prompted the addition of laparoscopic surgery to this recommendation. In that study, VTE occurred by 4 weeks in nearly 10% of patients receiving 1 week of prophylaxis and in no patients in the 4-week arm. Major bleeding occurred in one versus zero patients in the thromboprophylaxis arms, respectively (Ann Surg. April 2014;259[4]:665-9).
 

Reaffirmed recommendations

Based on the latest available data, the panel reaffirmed that most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis for the duration of their hospitalization and that thromboprophylaxis should not be routinely recommended for all outpatients with cancer.

The panel also reaffirmed the need for thromboprophylaxis starting preoperatively and continuing for at least 7-10 days in patients undergoing major cancer surgery, the need for periodic assessment of VTE risk in cancer patients, and the importance of patient education about the signs and symptoms of VTE.
 

Perspective and future directions

In an interview, David H. Henry, MD, said he was pleased to see ASCO incorporate the latest DOAC data into the VTE guideline.

The AVERT and CASSINI studies, in particular, highlight the value of using the Khorana Risk Score, which considers cancer type, blood counts, and body mass index to predict the risk of thrombosis in cancer patients and to guide decisions regarding prophylaxis, said Dr. Henry, vice chair of the department of medicine and clinical professor of medicine at Penn Medicine’s Abramson Cancer Center, Philadelphia.

The DOACs also represent “a nice new development in the treatment setting,” he said, adding that it’s been long known – since the 2003 CLOT trial – that cancer patients with VTE had much lower recurrence rates with LMWH versus warfarin (Coumadin).

“Now fast forward to the modern era ... and DOACs now appear to be a good idea,” he said.

Dr. Henry also addressed the recommendation for expanded postoperative LMWH use.

“That I found interesting; I’m not sure what took them so long,” he said, explaining that National Comprehensive Cancer Network and European Society of Medical Oncology recommendations have long stated that, for patients with abdominal cancers who undergo abdominopelvic surgery, DVT prophylaxis should continue for 4 weeks.

Dr. Henry said that a survey at his center showed that those recommendations were “very poorly followed,” with surgeons giving 4 weeks of prophylaxis in just 5% of cases.

“The good news from our survey was that not many people had a VTE, despite not many people following the recommendations, but I must say I think our surgeons are catching on,” he said.

Overall, the updated guideline highlights the importance of considering the “cancer variable” when it comes to VTE prevention and treatment.

“We’ve known forever that when we diagnose a DVT or PE in the outpatient setting – and this is independent of cancer – that you should treat it. Add the cancer variable and we now know that we should worry and try to prevent the VTE in certain high-risk patients, and there are some drugs to do it with,” he said, adding that “you should worry about the person you’ve just provoked [with surgery] as well.”

An important question not addressed in the guideline update is the indefinite use of DOACs in cancer patients with ongoing risk, he said.

“When we see DVT or PE, we usually treat for 3 months – that’s the industry standard – and at the end of 3 months ... you do a time out and you say to yourself, ‘Was this person provoked?’ ” he said.

For example, if they took a long flight or if pregnancy was a factor, treatment can usually be safely stopped. However, in a cancer patient who still has cancer, the provocation continues, and the patient may require indefinite treatment.

Questions that remain involve defining “indefinite” and include whether (and which of) these drugs can be used indefinitely in such patients, Dr. Henry said.

Dr. Key reported receiving honoraria from Novo Nordisk, research funding to his institution from Baxter Biosciences, Grifols, and Pfizer, and serving as a consultant or advisor for Genentech, Roche, Uniqure, Seattle Genetics, and Shire Human Genetic Therapies. Numerous disclosures were also reported by other expert panel members.

[email protected]