Renal Cell Carcinoma

Checkpoint inhibitors got to melanoma, non–small cell lung cancer, and renal cell carcinoma patients quickly in clinical practice after Food and Drug Administration approval – usually within 4 months – but the patients treated in clinical settings tended to be older than those treated in trials, which has caused concern about whether real-world efficacy will prove to be the same, according to a study in JAMA Oncology.

“Such rapid adoption stands in contrast to older estimates that suggest it takes years or even decades for new treatments to be adopted,” wrote lead author Cary Gross, MD, professor of medicine at Yale University, New Haven, and his coauthors. “We found significant differences in age between patients treated in practice and those treated in trials, which highlights the need to clarify the risks and benefits of checkpoint inhibitors in general populations of patients.”

Researchers drew data on nivolumab and pembrolizumab use from the Flatiron Health longitudinal EHR database, which included 233 academic and community oncology practices. In each of the three disease cohorts, adoption was seen within 4 months for at least 60% of patients. Uptake was quickest for the melanoma patients, 76% of whom received a checkpoint inhibitor within 4 months, investigators wrote. Factors for the fast adoption could include high disease severity, a preference for novelty, perceived gains over existing treatments, and promotional activities, such as media reports and advertising directly to consumers, they wrote.

More patients in real-world practice were aged 65 years or older, ranging from as little as 61% at the lowest end of the range at one center to as much as 64% at the highest end at another. In the clinical trials, the percentage of patients aged 65 years or older ranged from 32% in one trial to 41% in another. Researchers wrote that these higher real-world rates are concerning because there are still questions regarding whether differences in immune responses will cause differences in efficacy between older and younger patients, as well as safety considerations among different age groups.

“Although data suggest that outcomes are similar between older and younger patients receiving anti–PD-1 agents for melanoma, there is little evidence to guide anti–PD-1 treatment of older patients with NSCLC [non–small cell lung cancer],” Dr. Gross and his coinvestigators wrote.

Investigators wrote that the findings are cause for caution.

“As FDA officials develop more flexible standards for approval, which the 21st Century Cures Act requires them to do, it is possible that many patients will receive drugs before much is known about clinical outcomes,” Dr. Gross said. “Further integrations of real-world evidence might allow the FDA to better assess the drugs that they approve on the basis of nonrepresentative trial participants.”

SOURCE: Gross C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0798.






 

Checkpoint inhibitors got to melanoma, non–small cell lung cancer, and renal cell carcinoma patients quickly in clinical practice after Food and Drug Administration approval – usually within 4 months – but the patients treated in clinical settings tended to be older than those treated in trials, which has caused concern about whether real-world efficacy will prove to be the same, according to a study in JAMA Oncology.

“Such rapid adoption stands in contrast to older estimates that suggest it takes years or even decades for new treatments to be adopted,” wrote lead author Cary Gross, MD, professor of medicine at Yale University, New Haven, and his coauthors. “We found significant differences in age between patients treated in practice and those treated in trials, which highlights the need to clarify the risks and benefits of checkpoint inhibitors in general populations of patients.”

Researchers drew data on nivolumab and pembrolizumab use from the Flatiron Health longitudinal EHR database, which included 233 academic and community oncology practices. In each of the three disease cohorts, adoption was seen within 4 months for at least 60% of patients. Uptake was quickest for the melanoma patients, 76% of whom received a checkpoint inhibitor within 4 months, investigators wrote. Factors for the fast adoption could include high disease severity, a preference for novelty, perceived gains over existing treatments, and promotional activities, such as media reports and advertising directly to consumers, they wrote.

More patients in real-world practice were aged 65 years or older, ranging from as little as 61% at the lowest end of the range at one center to as much as 64% at the highest end at another. In the clinical trials, the percentage of patients aged 65 years or older ranged from 32% in one trial to 41% in another. Researchers wrote that these higher real-world rates are concerning because there are still questions regarding whether differences in immune responses will cause differences in efficacy between older and younger patients, as well as safety considerations among different age groups.

“Although data suggest that outcomes are similar between older and younger patients receiving anti–PD-1 agents for melanoma, there is little evidence to guide anti–PD-1 treatment of older patients with NSCLC [non–small cell lung cancer],” Dr. Gross and his coinvestigators wrote.

Investigators wrote that the findings are cause for caution.

“As FDA officials develop more flexible standards for approval, which the 21st Century Cures Act requires them to do, it is possible that many patients will receive drugs before much is known about clinical outcomes,” Dr. Gross said. “Further integrations of real-world evidence might allow the FDA to better assess the drugs that they approve on the basis of nonrepresentative trial participants.”

SOURCE: Gross C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0798.






 

Checkpoint inhibitors got to melanoma, non–small cell lung cancer, and renal cell carcinoma patients quickly in clinical practice after Food and Drug Administration approval – usually within 4 months – but the patients treated in clinical settings tended to be older than those treated in trials, which has caused concern about whether real-world efficacy will prove to be the same, according to a study in JAMA Oncology.

“Such rapid adoption stands in contrast to older estimates that suggest it takes years or even decades for new treatments to be adopted,” wrote lead author Cary Gross, MD, professor of medicine at Yale University, New Haven, and his coauthors. “We found significant differences in age between patients treated in practice and those treated in trials, which highlights the need to clarify the risks and benefits of checkpoint inhibitors in general populations of patients.”

Researchers drew data on nivolumab and pembrolizumab use from the Flatiron Health longitudinal EHR database, which included 233 academic and community oncology practices. In each of the three disease cohorts, adoption was seen within 4 months for at least 60% of patients. Uptake was quickest for the melanoma patients, 76% of whom received a checkpoint inhibitor within 4 months, investigators wrote. Factors for the fast adoption could include high disease severity, a preference for novelty, perceived gains over existing treatments, and promotional activities, such as media reports and advertising directly to consumers, they wrote.

More patients in real-world practice were aged 65 years or older, ranging from as little as 61% at the lowest end of the range at one center to as much as 64% at the highest end at another. In the clinical trials, the percentage of patients aged 65 years or older ranged from 32% in one trial to 41% in another. Researchers wrote that these higher real-world rates are concerning because there are still questions regarding whether differences in immune responses will cause differences in efficacy between older and younger patients, as well as safety considerations among different age groups.

“Although data suggest that outcomes are similar between older and younger patients receiving anti–PD-1 agents for melanoma, there is little evidence to guide anti–PD-1 treatment of older patients with NSCLC [non–small cell lung cancer],” Dr. Gross and his coinvestigators wrote.

Investigators wrote that the findings are cause for caution.

“As FDA officials develop more flexible standards for approval, which the 21st Century Cures Act requires them to do, it is possible that many patients will receive drugs before much is known about clinical outcomes,” Dr. Gross said. “Further integrations of real-world evidence might allow the FDA to better assess the drugs that they approve on the basis of nonrepresentative trial participants.”

SOURCE: Gross C et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0798.






 

For adults with metastatic, treatment-naive renal clear cell carcinoma, an alternate (2 weeks on, 1 week off) oral sunitinib schedule might be more tolerable than the approved 4:2 schedule, according to the results of a single-arm, multicenter, phase 2 trial.

After a median follow-up of 17 months, 25% of 59 patients had experienced grade 3 fatigue, hand-foot syndrome, or diarrhea, 37% had required dose reductions, and only 10% had stopped treatment because of toxicity. Rates of treatment discontinuation and dose reduction compared favorably with those seen with the 4:2 schedule in the pivotal COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial (37% and 51%, respectively), reported Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his associates in the Journal of Clinical Oncology.

Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is standard first-line therapy for metastatic clear cell renal cell carcinoma. But side effects impede treatment, and moderate to severe diarrhea, fatigue, and hand-foot syndrome are especially hard to manage without dose-reducing or interrupting therapy. These and other toxicities tend to peak during the second half of the Food and Drug Administration–approved 4-week treatment cycle, the investigators noted. Building on retrospective studies that have reported less toxicity with an alternate 2:1 schedule, they powered their trial to test whether this schedule would produce grade 3 or worse diarrhea, fatigue, or hand-foot syndrome in no more than 15% of patients.

Despite missing this endpoint, “the initial 2:1 schedule and subsequent schedule and dose alterations ensured that 90% [of patients] could continue treatment and avoid protracted high-grade toxicities,” the investigators said. Sunitinib showed “robust” efficacy – a 57% overall response rate and 13.7-month median progression-free survival – even though most patients were intermediate risk (67%) or poor risk (10%), they added. The nonrandomized data support using the alternate 2:1 schedule to maintain quality of life and extend treatment duration, they concluded.

Pfizer makes sunitinib and funded the study. Dr. Jonasch disclosed research funding, travel reimbursement, and an advisory relationship with Pfizer.
 

SOURCE: Jonasch E et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO.2017.77.1485.

For adults with metastatic, treatment-naive renal clear cell carcinoma, an alternate (2 weeks on, 1 week off) oral sunitinib schedule might be more tolerable than the approved 4:2 schedule, according to the results of a single-arm, multicenter, phase 2 trial.

After a median follow-up of 17 months, 25% of 59 patients had experienced grade 3 fatigue, hand-foot syndrome, or diarrhea, 37% had required dose reductions, and only 10% had stopped treatment because of toxicity. Rates of treatment discontinuation and dose reduction compared favorably with those seen with the 4:2 schedule in the pivotal COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial (37% and 51%, respectively), reported Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his associates in the Journal of Clinical Oncology.

Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is standard first-line therapy for metastatic clear cell renal cell carcinoma. But side effects impede treatment, and moderate to severe diarrhea, fatigue, and hand-foot syndrome are especially hard to manage without dose-reducing or interrupting therapy. These and other toxicities tend to peak during the second half of the Food and Drug Administration–approved 4-week treatment cycle, the investigators noted. Building on retrospective studies that have reported less toxicity with an alternate 2:1 schedule, they powered their trial to test whether this schedule would produce grade 3 or worse diarrhea, fatigue, or hand-foot syndrome in no more than 15% of patients.

Despite missing this endpoint, “the initial 2:1 schedule and subsequent schedule and dose alterations ensured that 90% [of patients] could continue treatment and avoid protracted high-grade toxicities,” the investigators said. Sunitinib showed “robust” efficacy – a 57% overall response rate and 13.7-month median progression-free survival – even though most patients were intermediate risk (67%) or poor risk (10%), they added. The nonrandomized data support using the alternate 2:1 schedule to maintain quality of life and extend treatment duration, they concluded.

Pfizer makes sunitinib and funded the study. Dr. Jonasch disclosed research funding, travel reimbursement, and an advisory relationship with Pfizer.
 

SOURCE: Jonasch E et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO.2017.77.1485.

For adults with metastatic, treatment-naive renal clear cell carcinoma, an alternate (2 weeks on, 1 week off) oral sunitinib schedule might be more tolerable than the approved 4:2 schedule, according to the results of a single-arm, multicenter, phase 2 trial.

After a median follow-up of 17 months, 25% of 59 patients had experienced grade 3 fatigue, hand-foot syndrome, or diarrhea, 37% had required dose reductions, and only 10% had stopped treatment because of toxicity. Rates of treatment discontinuation and dose reduction compared favorably with those seen with the 4:2 schedule in the pivotal COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial (37% and 51%, respectively), reported Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his associates in the Journal of Clinical Oncology.

Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is standard first-line therapy for metastatic clear cell renal cell carcinoma. But side effects impede treatment, and moderate to severe diarrhea, fatigue, and hand-foot syndrome are especially hard to manage without dose-reducing or interrupting therapy. These and other toxicities tend to peak during the second half of the Food and Drug Administration–approved 4-week treatment cycle, the investigators noted. Building on retrospective studies that have reported less toxicity with an alternate 2:1 schedule, they powered their trial to test whether this schedule would produce grade 3 or worse diarrhea, fatigue, or hand-foot syndrome in no more than 15% of patients.

Despite missing this endpoint, “the initial 2:1 schedule and subsequent schedule and dose alterations ensured that 90% [of patients] could continue treatment and avoid protracted high-grade toxicities,” the investigators said. Sunitinib showed “robust” efficacy – a 57% overall response rate and 13.7-month median progression-free survival – even though most patients were intermediate risk (67%) or poor risk (10%), they added. The nonrandomized data support using the alternate 2:1 schedule to maintain quality of life and extend treatment duration, they concluded.

Pfizer makes sunitinib and funded the study. Dr. Jonasch disclosed research funding, travel reimbursement, and an advisory relationship with Pfizer.
 

SOURCE: Jonasch E et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO.2017.77.1485.

A second interim analysis of data from the phase 3 ADAPT trial for the treatment of newly diagnosed metastatic renal cell carcinoma has led to discontinuation of the trial.

In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.

In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.

In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).

Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.

Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.

[email protected]

A second interim analysis of data from the phase 3 ADAPT trial for the treatment of newly diagnosed metastatic renal cell carcinoma has led to discontinuation of the trial.

In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.

In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.

In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).

Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.

Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.

[email protected]

A second interim analysis of data from the phase 3 ADAPT trial for the treatment of newly diagnosed metastatic renal cell carcinoma has led to discontinuation of the trial.

In ADAPT, 462 patients with previously untreated advanced or metastatic renal cell carcinoma (mRCC) were randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib versus sunitinib monotherapy, after undergoing cytoreductive nephrectomy.

In February 2017, the trial’s Independent Data Monitoring Committee had reviewed the data and concluded that the trial was unlikely to demonstrate a statistically significant improvement in median overall survival in the combination arm and recommended halting the trial. However, the principal investigators and the company, Argos Therapeutics, considered the data too immature to observe the delayed effects associated with immunotherapy and decided to continue the trial. They submitted a protocol amendment to the Food and Drug Administration adding additional co-primary endpoints, and in April of last year, met with the Food and Drug Administration, which accepted the amendment and agreed to continuation of the trial, according to a company press release issued in November.

In the latest interim analysis, which was conducted following an additional 51 deaths, median overall survival for the intent-to-treat patient population was 28.2 months for the combination arm (95% confidence interval, 23.4, 35.2) compared with 31.2 months (95% CI, 23.0, 44.5) for the control arm; this was one of four new co-primary endpoints. The hazard ratio was 1.10 (95% CI, 0.85, 1.42).

Other co-primary endpoints that were evaluated, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, did not demonstrate a favorable result, Argos Therapeutics said in a recent press release.

Rocapuldencel-T “consists of autologous dendritic cells programmed with amplified RNA from a patient’s primary tumor” and is “designed to overcome immunosuppression and induce broadly reactive, long-lasting anti-tumor memory T cells” according to the early interim analysis presented at the European Society for Medical Oncology (ESMO) 2017. The drug is also being evaluated in non–small cell lung cancer and bladder cancer.

[email protected]

The Food and Drug Administration has granted approvals to checkpoint inhibitors nivolumab and ipilimumab in combination for the treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma.

The approvals were based on statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination of nivolumab and ipilimumab (n = 425), compared with those receiving sunitinib (n = 422) in CheckMate 214, the FDA said in a press statement.

[email protected]

The Food and Drug Administration has granted approvals to checkpoint inhibitors nivolumab and ipilimumab in combination for the treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma.

The approvals were based on statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination of nivolumab and ipilimumab (n = 425), compared with those receiving sunitinib (n = 422) in CheckMate 214, the FDA said in a press statement.

[email protected]

The Food and Drug Administration has granted approvals to checkpoint inhibitors nivolumab and ipilimumab in combination for the treatment of intermediate- or poor-risk, previously untreated advanced renal cell carcinoma.

The approvals were based on statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination of nivolumab and ipilimumab (n = 425), compared with those receiving sunitinib (n = 422) in CheckMate 214, the FDA said in a press statement.

[email protected]

Physicians receiving general payments from the company marketing a targeted cancer therapy were more likely to prescribe it in three out of six drugs evaluated, researchers reported.

Prescribing of sunitinib, dasatinib, and nilotinib was increased for physicians receiving such payments versus not receiving them, while prescribing of imatinib, sorafenib, and pazopanib were not, according to the analysis by Aaron P. Mitchell, MD, of the Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, and his coauthors.

In previous studies, pharmaceutical industry payments to physicians have been associated with “higher-cost, brand-name pharmaceutical prescribing,” Dr. Mitchell and his colleagues wrote. The report was published in JAMA Internal Medicine.

“Whether industry payments are associated with physician treatment choice in oncology is uncertain,” they said.

To evaluate the association between payments to oncologists and drug selection, Dr. Mitchell and his colleagues linked Open Payments data from the Centers for Medicare & Medicaid Services to data from Medicare Part D Prescriber Public Use File for the years 2013-2014.

The primary variable in the study was payments received during 2013, according to investigators, and the primary outcome of the analysis was prescriptions filled during 2014.

Open Payments reported in 2013 had a total dollar value of $4.08 billion, including $1.20 billion paid to physicians, according to CMS data.

The researchers focused on targeted therapies for two therapeutic areas: metastatic renal cell carcinoma (RCC), including sorafenib, sunitinib, and pazopanib; and chronic myeloid leukemia (CML), including imatinib, dasatinib, and nilotinib.

They limited their analysis to physicians listed as oncologists who filled at least 20 prescriptions for each of the three drugs in metastatic RCC (n = 354) or in CML (n = 2,225).

Receiving payments categorized as “general,” such as gifts, speaker fees, meals, and travel, increased the odds of prescribing drugs for both metastatic RCC (odds ratio, 2.05; 95% confidence interval, 1.34-3.14; P = .001) and for CML (odds ratio, 1.29; 95% CI, 1.13-1.47; P less than .001).

By contrast, research payments did not increase the odds of prescribing those drugs, the investigators reported.

Looking at specific drugs, they found that receipt of general payments from a drug’s manufacturer was associated with increased prescribing of sunitinib (50.5% versus 34.4%, P = .01), dasatinib (13.8% versus 11.4%, P = .02), and nilotinib (15.4% vs 12.5%, P = .01).

However, no such association was found for sorafenib or pazopanib.

For imatinib, by contrast, investigators said industry payments were associated with a prescribing decrease.

“This may reflect a strategy by the manufacturer of imatinib, which also produces nilotinib, to promote switching to nilotinib before the patent expiration of imatinib in 2015,” the researchers wrote.

Dr. Mitchell and his coauthors reported no conflict of interest disclosures related to the study.

SOURCE: Mitchell AP, et al. JAMA Intern Med. 2018 Apr 9. doi: 0.1001/jamainternmed.2018.0776.

Physicians receiving general payments from the company marketing a targeted cancer therapy were more likely to prescribe it in three out of six drugs evaluated, researchers reported.

Prescribing of sunitinib, dasatinib, and nilotinib was increased for physicians receiving such payments versus not receiving them, while prescribing of imatinib, sorafenib, and pazopanib were not, according to the analysis by Aaron P. Mitchell, MD, of the Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, and his coauthors.

In previous studies, pharmaceutical industry payments to physicians have been associated with “higher-cost, brand-name pharmaceutical prescribing,” Dr. Mitchell and his colleagues wrote. The report was published in JAMA Internal Medicine.

“Whether industry payments are associated with physician treatment choice in oncology is uncertain,” they said.

To evaluate the association between payments to oncologists and drug selection, Dr. Mitchell and his colleagues linked Open Payments data from the Centers for Medicare & Medicaid Services to data from Medicare Part D Prescriber Public Use File for the years 2013-2014.

The primary variable in the study was payments received during 2013, according to investigators, and the primary outcome of the analysis was prescriptions filled during 2014.

Open Payments reported in 2013 had a total dollar value of $4.08 billion, including $1.20 billion paid to physicians, according to CMS data.

The researchers focused on targeted therapies for two therapeutic areas: metastatic renal cell carcinoma (RCC), including sorafenib, sunitinib, and pazopanib; and chronic myeloid leukemia (CML), including imatinib, dasatinib, and nilotinib.

They limited their analysis to physicians listed as oncologists who filled at least 20 prescriptions for each of the three drugs in metastatic RCC (n = 354) or in CML (n = 2,225).

Receiving payments categorized as “general,” such as gifts, speaker fees, meals, and travel, increased the odds of prescribing drugs for both metastatic RCC (odds ratio, 2.05; 95% confidence interval, 1.34-3.14; P = .001) and for CML (odds ratio, 1.29; 95% CI, 1.13-1.47; P less than .001).

By contrast, research payments did not increase the odds of prescribing those drugs, the investigators reported.

Looking at specific drugs, they found that receipt of general payments from a drug’s manufacturer was associated with increased prescribing of sunitinib (50.5% versus 34.4%, P = .01), dasatinib (13.8% versus 11.4%, P = .02), and nilotinib (15.4% vs 12.5%, P = .01).

However, no such association was found for sorafenib or pazopanib.

For imatinib, by contrast, investigators said industry payments were associated with a prescribing decrease.

“This may reflect a strategy by the manufacturer of imatinib, which also produces nilotinib, to promote switching to nilotinib before the patent expiration of imatinib in 2015,” the researchers wrote.

Dr. Mitchell and his coauthors reported no conflict of interest disclosures related to the study.

SOURCE: Mitchell AP, et al. JAMA Intern Med. 2018 Apr 9. doi: 0.1001/jamainternmed.2018.0776.

Physicians receiving general payments from the company marketing a targeted cancer therapy were more likely to prescribe it in three out of six drugs evaluated, researchers reported.

Prescribing of sunitinib, dasatinib, and nilotinib was increased for physicians receiving such payments versus not receiving them, while prescribing of imatinib, sorafenib, and pazopanib were not, according to the analysis by Aaron P. Mitchell, MD, of the Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, and his coauthors.

In previous studies, pharmaceutical industry payments to physicians have been associated with “higher-cost, brand-name pharmaceutical prescribing,” Dr. Mitchell and his colleagues wrote. The report was published in JAMA Internal Medicine.

“Whether industry payments are associated with physician treatment choice in oncology is uncertain,” they said.

To evaluate the association between payments to oncologists and drug selection, Dr. Mitchell and his colleagues linked Open Payments data from the Centers for Medicare & Medicaid Services to data from Medicare Part D Prescriber Public Use File for the years 2013-2014.

The primary variable in the study was payments received during 2013, according to investigators, and the primary outcome of the analysis was prescriptions filled during 2014.

Open Payments reported in 2013 had a total dollar value of $4.08 billion, including $1.20 billion paid to physicians, according to CMS data.

The researchers focused on targeted therapies for two therapeutic areas: metastatic renal cell carcinoma (RCC), including sorafenib, sunitinib, and pazopanib; and chronic myeloid leukemia (CML), including imatinib, dasatinib, and nilotinib.

They limited their analysis to physicians listed as oncologists who filled at least 20 prescriptions for each of the three drugs in metastatic RCC (n = 354) or in CML (n = 2,225).

Receiving payments categorized as “general,” such as gifts, speaker fees, meals, and travel, increased the odds of prescribing drugs for both metastatic RCC (odds ratio, 2.05; 95% confidence interval, 1.34-3.14; P = .001) and for CML (odds ratio, 1.29; 95% CI, 1.13-1.47; P less than .001).

By contrast, research payments did not increase the odds of prescribing those drugs, the investigators reported.

Looking at specific drugs, they found that receipt of general payments from a drug’s manufacturer was associated with increased prescribing of sunitinib (50.5% versus 34.4%, P = .01), dasatinib (13.8% versus 11.4%, P = .02), and nilotinib (15.4% vs 12.5%, P = .01).

However, no such association was found for sorafenib or pazopanib.

For imatinib, by contrast, investigators said industry payments were associated with a prescribing decrease.

“This may reflect a strategy by the manufacturer of imatinib, which also produces nilotinib, to promote switching to nilotinib before the patent expiration of imatinib in 2015,” the researchers wrote.

Dr. Mitchell and his coauthors reported no conflict of interest disclosures related to the study.

SOURCE: Mitchell AP, et al. JAMA Intern Med. 2018 Apr 9. doi: 0.1001/jamainternmed.2018.0776.

CHICAGO – Cancer patients don’t necessarily have to come off immune checkpoint inhibitors if they develop diabetes, according to Priyanka Iyer, MD, an endocrinology fellow at MD Anderson Cancer Center, Houston.

“As long as we get glycemic control, they can continue,” she said at the annual meeting of the Endocrine Society.

Diabetes is a known side effect of immune checkpoint inhibitors (ICIs) but it’s rare, occurring in maybe 0.17% of patients, and its natural history and risk factors are unknown.

Median time to diabetes presentation after the start of ICI treatment was 12.3 weeks but ranged from 1 to 67.2 weeks. Half of the cases presented in diabetic ketoacidosis (DKA). Patients had upward trending hyperglycemia and most had diabetes symptoms for a while before diagnosis. They presented with a blood glucose above 250 mg/dL, and more than half above 500 mg/dL. Median hemoglobin A_1c at presentation was 8%, but ranged up to 12.5%.

Every patient required insulin, including the six that discontinued ICIs after developing diabetes. Diabetes resolved in just one patient at 10.2 months; she presented with DKA.

There were no obvious predisposing factors. None of the patients had histories of type 1 diabetes or other autoimmune disease. Five patients had well-controlled type 2 diabetes prior to ICI initiation; four had prediabetes. Some had family members with type 2 diabetes, but not type 1. Four had prior ICI exposure. Just three patients were on concomitant steroids.

A few patients also developed thyroid or pituitary dysfunction, which are more common side effects of ICIs.

The median age at diabetes presentation was 61 years and ranged from 32 to 82 years. The majority of patients were men, which reflects MD Anderson demographics, not a predisposing risk factor, Dr. Iyer said.

Melanoma was the most common cancer, followed by renal cell and prostate; patients had stage 2-4 disease. About half the subjects were on single agent anti-PD-1 treatment, about a third on anti-PD-1 combination treatment, and the rest on anti-PD-L1 combination therapy. C-peptide levels were below 0.9 ng/mL at diabetes diagnosis in most of the patients. Eleven of the 20 tested (55%) were positive for the pancreatic islet cell antibody GAD65.

The investigators had no disclosures. A funding source was not reported.

[email protected]

SOURCE: Iyer PC et al. Abstract OR05-5.

CHICAGO – Cancer patients don’t necessarily have to come off immune checkpoint inhibitors if they develop diabetes, according to Priyanka Iyer, MD, an endocrinology fellow at MD Anderson Cancer Center, Houston.

“As long as we get glycemic control, they can continue,” she said at the annual meeting of the Endocrine Society.

Diabetes is a known side effect of immune checkpoint inhibitors (ICIs) but it’s rare, occurring in maybe 0.17% of patients, and its natural history and risk factors are unknown.

Median time to diabetes presentation after the start of ICI treatment was 12.3 weeks but ranged from 1 to 67.2 weeks. Half of the cases presented in diabetic ketoacidosis (DKA). Patients had upward trending hyperglycemia and most had diabetes symptoms for a while before diagnosis. They presented with a blood glucose above 250 mg/dL, and more than half above 500 mg/dL. Median hemoglobin A_1c at presentation was 8%, but ranged up to 12.5%.

Every patient required insulin, including the six that discontinued ICIs after developing diabetes. Diabetes resolved in just one patient at 10.2 months; she presented with DKA.

There were no obvious predisposing factors. None of the patients had histories of type 1 diabetes or other autoimmune disease. Five patients had well-controlled type 2 diabetes prior to ICI initiation; four had prediabetes. Some had family members with type 2 diabetes, but not type 1. Four had prior ICI exposure. Just three patients were on concomitant steroids.

A few patients also developed thyroid or pituitary dysfunction, which are more common side effects of ICIs.

The median age at diabetes presentation was 61 years and ranged from 32 to 82 years. The majority of patients were men, which reflects MD Anderson demographics, not a predisposing risk factor, Dr. Iyer said.

Melanoma was the most common cancer, followed by renal cell and prostate; patients had stage 2-4 disease. About half the subjects were on single agent anti-PD-1 treatment, about a third on anti-PD-1 combination treatment, and the rest on anti-PD-L1 combination therapy. C-peptide levels were below 0.9 ng/mL at diabetes diagnosis in most of the patients. Eleven of the 20 tested (55%) were positive for the pancreatic islet cell antibody GAD65.

The investigators had no disclosures. A funding source was not reported.

[email protected]

SOURCE: Iyer PC et al. Abstract OR05-5.

CHICAGO – Cancer patients don’t necessarily have to come off immune checkpoint inhibitors if they develop diabetes, according to Priyanka Iyer, MD, an endocrinology fellow at MD Anderson Cancer Center, Houston.

“As long as we get glycemic control, they can continue,” she said at the annual meeting of the Endocrine Society.

Diabetes is a known side effect of immune checkpoint inhibitors (ICIs) but it’s rare, occurring in maybe 0.17% of patients, and its natural history and risk factors are unknown.

Median time to diabetes presentation after the start of ICI treatment was 12.3 weeks but ranged from 1 to 67.2 weeks. Half of the cases presented in diabetic ketoacidosis (DKA). Patients had upward trending hyperglycemia and most had diabetes symptoms for a while before diagnosis. They presented with a blood glucose above 250 mg/dL, and more than half above 500 mg/dL. Median hemoglobin A_1c at presentation was 8%, but ranged up to 12.5%.

Every patient required insulin, including the six that discontinued ICIs after developing diabetes. Diabetes resolved in just one patient at 10.2 months; she presented with DKA.

There were no obvious predisposing factors. None of the patients had histories of type 1 diabetes or other autoimmune disease. Five patients had well-controlled type 2 diabetes prior to ICI initiation; four had prediabetes. Some had family members with type 2 diabetes, but not type 1. Four had prior ICI exposure. Just three patients were on concomitant steroids.

A few patients also developed thyroid or pituitary dysfunction, which are more common side effects of ICIs.

The median age at diabetes presentation was 61 years and ranged from 32 to 82 years. The majority of patients were men, which reflects MD Anderson demographics, not a predisposing risk factor, Dr. Iyer said.

Melanoma was the most common cancer, followed by renal cell and prostate; patients had stage 2-4 disease. About half the subjects were on single agent anti-PD-1 treatment, about a third on anti-PD-1 combination treatment, and the rest on anti-PD-L1 combination therapy. C-peptide levels were below 0.9 ng/mL at diabetes diagnosis in most of the patients. Eleven of the 20 tested (55%) were positive for the pancreatic islet cell antibody GAD65.

The investigators had no disclosures. A funding source was not reported.

[email protected]

SOURCE: Iyer PC et al. Abstract OR05-5.

For patients with advanced renal cell carcinoma (RCC) progressing after sorafenib treatment, tivozanib was well tolerated and provided promising survival outcomes, investigators in a phase 2 study have reported.

Incidence of adverse events on tivozanib was low, and the safety profile was favorable in comparison with other agents in its class, the investigators said in the European Journal of Cancer.

The findings also help clarify results of a previous randomized phase 3 trial of tivozanib versus sorafenib where the investigators say crossover may have confounded overall survival results to the detriment of the tivozanib arm.

“Collectively, these data provide evidence of the anti-tumor activity of tivozanib and may be used to help frame future studies in recurrent disease,” wrote Ana M. Molina, MD, of Weill Cornell Medicine, New York, and her coauthors.

Tivozanib, recently approved in Europe for untreated RCC, is characterized by highly potent and selective inhibition of the three known vascular endothelial growth factor (VEGF) receptors.

Dr. Molina and her colleagues reported a single-arm crossover study of patients who were previously enrolled in the randomized phase 3 TIVO-1 trial of tivozanib versus sorafenib.

They enrolled a total of 161 patients who were randomized to the sorafenib arm of TIVO-1 and went on to receive tivozanib after disease progression.

Median progression-free survival was 11.0 months and median overall survival was 21.6 months for these crossover patients, Dr. Molina and co-investigators reported.

No patients in the study had a complete response, while 29 (18%) had a partial response and 83 (52%) had stable disease.

“These data compare favorably with other second-line therapies for RCC,” Dr. Molina and co-authors said.

Grade 3 or greater adverse events occurred in 48% of patients, including 24% that were treatment related. The most common grade 3 treatment-related adverse event was hypertension in 11%.

Approximately 4% of patients discontinued tivozanib due to adverse events.

“This study also provided clarity of the TIVO-1 trial, in which patient crossover was thought to have confounded the overall survival results,” Dr. Molina and colleagues said.

In TIVO-1, the primary end point of progression-free survival was improved for tivozanib versus sorafenib (median of 11.9 vs 9.1 months; P = .042), they noted.

However, median overall survival was not statistically different between arms, possibly because 74% of patients randomized to sorafenib were treated with next-line therapy, mainly tivozanib, investigators said.

AVEO Oncology and Astellas Pharma US, Inc. funded the study. Dr. Molina reported receiving honoraria from AVEO, Novartis, and Eisai.

SOURCE: Molina AM, et al. Eur J Cancer. 2018 Mar 13. doi: 10.1016/j.ejca.2018.02.009.

For patients with advanced renal cell carcinoma (RCC) progressing after sorafenib treatment, tivozanib was well tolerated and provided promising survival outcomes, investigators in a phase 2 study have reported.

Incidence of adverse events on tivozanib was low, and the safety profile was favorable in comparison with other agents in its class, the investigators said in the European Journal of Cancer.

The findings also help clarify results of a previous randomized phase 3 trial of tivozanib versus sorafenib where the investigators say crossover may have confounded overall survival results to the detriment of the tivozanib arm.

“Collectively, these data provide evidence of the anti-tumor activity of tivozanib and may be used to help frame future studies in recurrent disease,” wrote Ana M. Molina, MD, of Weill Cornell Medicine, New York, and her coauthors.

Tivozanib, recently approved in Europe for untreated RCC, is characterized by highly potent and selective inhibition of the three known vascular endothelial growth factor (VEGF) receptors.

Dr. Molina and her colleagues reported a single-arm crossover study of patients who were previously enrolled in the randomized phase 3 TIVO-1 trial of tivozanib versus sorafenib.

They enrolled a total of 161 patients who were randomized to the sorafenib arm of TIVO-1 and went on to receive tivozanib after disease progression.

Median progression-free survival was 11.0 months and median overall survival was 21.6 months for these crossover patients, Dr. Molina and co-investigators reported.

No patients in the study had a complete response, while 29 (18%) had a partial response and 83 (52%) had stable disease.

“These data compare favorably with other second-line therapies for RCC,” Dr. Molina and co-authors said.

Grade 3 or greater adverse events occurred in 48% of patients, including 24% that were treatment related. The most common grade 3 treatment-related adverse event was hypertension in 11%.

Approximately 4% of patients discontinued tivozanib due to adverse events.

“This study also provided clarity of the TIVO-1 trial, in which patient crossover was thought to have confounded the overall survival results,” Dr. Molina and colleagues said.

In TIVO-1, the primary end point of progression-free survival was improved for tivozanib versus sorafenib (median of 11.9 vs 9.1 months; P = .042), they noted.

However, median overall survival was not statistically different between arms, possibly because 74% of patients randomized to sorafenib were treated with next-line therapy, mainly tivozanib, investigators said.

AVEO Oncology and Astellas Pharma US, Inc. funded the study. Dr. Molina reported receiving honoraria from AVEO, Novartis, and Eisai.

SOURCE: Molina AM, et al. Eur J Cancer. 2018 Mar 13. doi: 10.1016/j.ejca.2018.02.009.

For patients with advanced renal cell carcinoma (RCC) progressing after sorafenib treatment, tivozanib was well tolerated and provided promising survival outcomes, investigators in a phase 2 study have reported.

Incidence of adverse events on tivozanib was low, and the safety profile was favorable in comparison with other agents in its class, the investigators said in the European Journal of Cancer.

The findings also help clarify results of a previous randomized phase 3 trial of tivozanib versus sorafenib where the investigators say crossover may have confounded overall survival results to the detriment of the tivozanib arm.

“Collectively, these data provide evidence of the anti-tumor activity of tivozanib and may be used to help frame future studies in recurrent disease,” wrote Ana M. Molina, MD, of Weill Cornell Medicine, New York, and her coauthors.

Tivozanib, recently approved in Europe for untreated RCC, is characterized by highly potent and selective inhibition of the three known vascular endothelial growth factor (VEGF) receptors.

Dr. Molina and her colleagues reported a single-arm crossover study of patients who were previously enrolled in the randomized phase 3 TIVO-1 trial of tivozanib versus sorafenib.

They enrolled a total of 161 patients who were randomized to the sorafenib arm of TIVO-1 and went on to receive tivozanib after disease progression.

Median progression-free survival was 11.0 months and median overall survival was 21.6 months for these crossover patients, Dr. Molina and co-investigators reported.

No patients in the study had a complete response, while 29 (18%) had a partial response and 83 (52%) had stable disease.

“These data compare favorably with other second-line therapies for RCC,” Dr. Molina and co-authors said.

Grade 3 or greater adverse events occurred in 48% of patients, including 24% that were treatment related. The most common grade 3 treatment-related adverse event was hypertension in 11%.

Approximately 4% of patients discontinued tivozanib due to adverse events.

“This study also provided clarity of the TIVO-1 trial, in which patient crossover was thought to have confounded the overall survival results,” Dr. Molina and colleagues said.

In TIVO-1, the primary end point of progression-free survival was improved for tivozanib versus sorafenib (median of 11.9 vs 9.1 months; P = .042), they noted.

However, median overall survival was not statistically different between arms, possibly because 74% of patients randomized to sorafenib were treated with next-line therapy, mainly tivozanib, investigators said.

AVEO Oncology and Astellas Pharma US, Inc. funded the study. Dr. Molina reported receiving honoraria from AVEO, Novartis, and Eisai.

SOURCE: Molina AM, et al. Eur J Cancer. 2018 Mar 13. doi: 10.1016/j.ejca.2018.02.009.

The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.

More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.

The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.

“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.

SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.

The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.

More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.

The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.

“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.

SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.

The combination of axitinib and avelumab had manageable toxicity and demonstrated preliminary efficacy as a front-line treatment of advanced renal cell carcinoma (RCC), according to results of a recent study.

More than half of patients had a response on the combination of axitinib (Inlyta), a receptor inhibitor of vascular endothelial growth factor (VEGF), and avelumab (Bavencio), an anti-PD-L1 monoclonal antibody, investigators reported in The Lancet Oncology.

The most common treatment-related adverse event was hypertension, wrote lead author Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, and his colleagues.

“The combination of avelumab and axitinib in treatment-naive patients with advanced RCC had a manageable safety profile consistent with the profiles of the individual agents when administered as monotherapy, and antitumor activity was encouraging,” said Dr. Choueiri, and his colleagues.

SOURCE: Choueiri TK et al. Lancet Oncol. 2018 Mar 9. doi: 10.1016/S1470-2045(18)30107-4.

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

When a standardized radiologic threshold of greater than 50% is used, patients with unifocal cystic renal cell carcinoma (cRCC) have an excellent prognosis with active surveillance and following surgical resection, findings from a new study show.

At a median follow-up of 5.4 years (IQR 2.8-7.8), none of the 138 patients in the cohort experienced a tumor recurrence or metastasis from cRCC, and 7 (5.1%) died from non–renal-related causes. When comparing patients who initially underwent surgery to those who were initially managed with active surveillance, the researchers found that there was no significant difference in overall survival (P = .07). There were no deaths due to kidney cancer in the entire cohort.

The terminology of cRCC has historically been used to describe an indolent version of RCC that consists primarily of cysts, and the threshold of cystic involvement has traditionally been greater than 75% cystic on pathologic examination.

However, this classification does not contribute to the preoperative decision-making process, the study authors noted in Journal of Urology.

“Cross-sectional imaging provides the benefit of assessing tumor morphology without surgical manipulation, allowing for an accurate assessment of the solid and cystic components and classification of cRCC ,” write Ari Hakimi, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.

Studies evaluating radiologic criteria for cRCC diagnosis have suggested that cystic changes in 5%-45% of the total mass observed on imaging are associated with favorable survival. Thus, the authors sought to improve the preoperative assessment of cystic renal masses by evaluating cRCC as an enhancing renal lesion that is greater than 50% cystic on cross-sectional imaging. The goal of the current study was then to compare the long-term outcomes of patients with cRCC who underwent surgery and active surveillance using this hypothesized threshold.

The cohort included 138 patients who underwent surgery at Memorial Sloan Kettering Cancer Center for a renal mass from January 2000 to December 2015, and of this group, 102 (73.9%) had renal cell carcinoma and 36 (26.1%) had benign masses. Most of the tumors were Fuhrman grade 1-2 (77.5%), ≤pT2 stage (83.4%) and clear cell histology (65.9%), while the majority of cRCC lesions were Bosniak 3 and 4 (93.5%) and had a solid component of less than 25% (83.3%). On multivariate analysis, men (P = .007) were more likely to have malignant lesions and Bosniak 3 lesions were more likely to be malignant (P = .01).

In the subgroup of 38 active surveillance patients, 27 (71.1%) remained on active surveillance while 11 (28.9%) subsequently had surgery, of which all underwent partial nephrectomy. The median overall growth rate for lesions was 1.0 mm/year (IQR 0-2.8) over 25.3 months (IQR 16.3-44.8), and no evidence of recurrence or metastasis was reported in any of these patients at a median follow-up of 4.3 years (IQR 2.1-5.7) from first imaging diagnosis or 6.9 years (IQR 4.9-8.5) after surgery.

“We believe that our radiologic definition allows for more inclusive criteria of cRCC and would encourage kidney sparing approaches or implementation of AS protocols when feasible,” the authors concluded.

SOURCE: Hakimi A et al. J Urol. 2018 Feb 26 doi: 10.1016/j.juro.2018.02.3087

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.