Renal Cell Carcinoma

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.

A combination of the tyrosine kinase inhibitor axitinib (Inlyta) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was associated with acceptable toxicities and showed promising activity against advanced renal cell carcinoma (RCC) in the first-line setting, results of a phase 1b trial indicate.

Of 11 patients enrolled in a dose-finding study and 41 enrolled in the expansion phase of that study, 38 had an objective response (complete or partial response), for an overall response rate of 73%, reported Michael B. Atkins, MD, of Georgetown-Lombardi Comprehensive Cancer Center, Washington, and his colleagues.

“This phase 1b study showed that the combination of axitinib and pembrolizumab at nearly the full planned doses of each drug is tolerable in patients with treatment-naive advanced renal cell carcinoma,” they wrote. The report was published in The Lancet Oncology.

Previous studies of programmed death-1 (PD-1) checkpoint inhibitors such as pembrolizumab or nivolumab (Opdivo) combined with inhibitors of vascular endothelial growth factor (VEGF) have resulted in excessive toxicities attributed to off-target effects of the VEGF inhibitors used.

The investigators reasoned that because axitinib is more selective and specific for targets in the VEGF pathway, it might make a safer and more effective partner to a PD-1 inhibitor than the multikinase inhibitors sunitinib (Sutent) or pazopanib (Votrient).

“A formal systematic review was not done before doing this trial because most of the work combining VEGF pathway inhibitors with checkpoint inhibitors is new and not yet published,” Dr. Atkins and his associates explained.

As of the March 31, 2017, data cutoff, 52 patients from 10 U.S. centers had been treated with the same dose and schedule and were included in the analysis. All patients had tumors with clear cell renal carcinoma histologies; one also had sarcomatoid features.

There were three investigator-assessed dose-limiting toxicities (DLT, the primary endpoint) in the 11 patients treated in the dose-finding phase. One of the patients had a transient ischemic attack and two completed less than 75% of the planned axitinib dose because of treatment-related toxicities.

Of the 52 patients, 25 were still on treatment at the time of data cutoff: 22 who were still receiving both axitinib and pembrolizumab and 3 who were receiving only the PD-1 inhibitor. Eight of the patients continued on therapy despite disease progression.

Of the 27 patients who discontinued both drugs, 10 did so because of adverse events, 9 for disease progression, and others for various reasons such as mixed adverse events and disease progression, investigator discretion, global deterioration, or protocol violation.

Grade 3 or greater adverse events occurred in 34 patients (65%), and included hypertension, diarrhea, fatigue, and elevated alanine aminostransferase (ALT) levels.

The most common potentially immune-related adverse events were diarrhea, ALT elevations, hypothyroidism, and fatigue.

At a median follow-up of 20.4 months, 4 patients had a complete response, and 34 had a partial response. An additional eight patients had stable disease. Responses were seen in 18 of 24 patients with favorable-risk disease and in 18 of 26 patients with intermediate- or poor-risk disease. The median time to response was 2.8 months, and the median duration of response was 18.6 months.
“Future research should focus on investigating the mechanism of the potential synergistic effects of axitinib and pembrolizumab, and whether an immunotherapy-only approach (including combinations) enriched by the appropriate biomarkers, followed by VEGFR TKI salvage, might produce more durable off-treatment responses or whether administering VEGFR TKI monotherapy followed by PD-1 and PD-L1 pathway blockade might produce superior or equivalent results,” the investigators concluded.

Pfizer, in collaboration with Merck, sponsored the study. Dr. Atkins and several coauthors disclosed consulting fees from Pfizer, Merck, and other companies. Four of the coauthors are Pfizer employees and stockholders.

[email protected]

SOURCE: Atkins MB et al. Lancet Oncol 2018 Feb. 10. doi: 10.1016/S1470-2045(18)30081-0.

A combination of the tyrosine kinase inhibitor axitinib (Inlyta) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was associated with acceptable toxicities and showed promising activity against advanced renal cell carcinoma (RCC) in the first-line setting, results of a phase 1b trial indicate.

Of 11 patients enrolled in a dose-finding study and 41 enrolled in the expansion phase of that study, 38 had an objective response (complete or partial response), for an overall response rate of 73%, reported Michael B. Atkins, MD, of Georgetown-Lombardi Comprehensive Cancer Center, Washington, and his colleagues.

“This phase 1b study showed that the combination of axitinib and pembrolizumab at nearly the full planned doses of each drug is tolerable in patients with treatment-naive advanced renal cell carcinoma,” they wrote. The report was published in The Lancet Oncology.

Previous studies of programmed death-1 (PD-1) checkpoint inhibitors such as pembrolizumab or nivolumab (Opdivo) combined with inhibitors of vascular endothelial growth factor (VEGF) have resulted in excessive toxicities attributed to off-target effects of the VEGF inhibitors used.

The investigators reasoned that because axitinib is more selective and specific for targets in the VEGF pathway, it might make a safer and more effective partner to a PD-1 inhibitor than the multikinase inhibitors sunitinib (Sutent) or pazopanib (Votrient).

“A formal systematic review was not done before doing this trial because most of the work combining VEGF pathway inhibitors with checkpoint inhibitors is new and not yet published,” Dr. Atkins and his associates explained.

As of the March 31, 2017, data cutoff, 52 patients from 10 U.S. centers had been treated with the same dose and schedule and were included in the analysis. All patients had tumors with clear cell renal carcinoma histologies; one also had sarcomatoid features.

There were three investigator-assessed dose-limiting toxicities (DLT, the primary endpoint) in the 11 patients treated in the dose-finding phase. One of the patients had a transient ischemic attack and two completed less than 75% of the planned axitinib dose because of treatment-related toxicities.

Of the 52 patients, 25 were still on treatment at the time of data cutoff: 22 who were still receiving both axitinib and pembrolizumab and 3 who were receiving only the PD-1 inhibitor. Eight of the patients continued on therapy despite disease progression.

Of the 27 patients who discontinued both drugs, 10 did so because of adverse events, 9 for disease progression, and others for various reasons such as mixed adverse events and disease progression, investigator discretion, global deterioration, or protocol violation.

Grade 3 or greater adverse events occurred in 34 patients (65%), and included hypertension, diarrhea, fatigue, and elevated alanine aminostransferase (ALT) levels.

The most common potentially immune-related adverse events were diarrhea, ALT elevations, hypothyroidism, and fatigue.

At a median follow-up of 20.4 months, 4 patients had a complete response, and 34 had a partial response. An additional eight patients had stable disease. Responses were seen in 18 of 24 patients with favorable-risk disease and in 18 of 26 patients with intermediate- or poor-risk disease. The median time to response was 2.8 months, and the median duration of response was 18.6 months.
“Future research should focus on investigating the mechanism of the potential synergistic effects of axitinib and pembrolizumab, and whether an immunotherapy-only approach (including combinations) enriched by the appropriate biomarkers, followed by VEGFR TKI salvage, might produce more durable off-treatment responses or whether administering VEGFR TKI monotherapy followed by PD-1 and PD-L1 pathway blockade might produce superior or equivalent results,” the investigators concluded.

Pfizer, in collaboration with Merck, sponsored the study. Dr. Atkins and several coauthors disclosed consulting fees from Pfizer, Merck, and other companies. Four of the coauthors are Pfizer employees and stockholders.

[email protected]

SOURCE: Atkins MB et al. Lancet Oncol 2018 Feb. 10. doi: 10.1016/S1470-2045(18)30081-0.

A combination of the tyrosine kinase inhibitor axitinib (Inlyta) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was associated with acceptable toxicities and showed promising activity against advanced renal cell carcinoma (RCC) in the first-line setting, results of a phase 1b trial indicate.

Of 11 patients enrolled in a dose-finding study and 41 enrolled in the expansion phase of that study, 38 had an objective response (complete or partial response), for an overall response rate of 73%, reported Michael B. Atkins, MD, of Georgetown-Lombardi Comprehensive Cancer Center, Washington, and his colleagues.

“This phase 1b study showed that the combination of axitinib and pembrolizumab at nearly the full planned doses of each drug is tolerable in patients with treatment-naive advanced renal cell carcinoma,” they wrote. The report was published in The Lancet Oncology.

Previous studies of programmed death-1 (PD-1) checkpoint inhibitors such as pembrolizumab or nivolumab (Opdivo) combined with inhibitors of vascular endothelial growth factor (VEGF) have resulted in excessive toxicities attributed to off-target effects of the VEGF inhibitors used.

The investigators reasoned that because axitinib is more selective and specific for targets in the VEGF pathway, it might make a safer and more effective partner to a PD-1 inhibitor than the multikinase inhibitors sunitinib (Sutent) or pazopanib (Votrient).

“A formal systematic review was not done before doing this trial because most of the work combining VEGF pathway inhibitors with checkpoint inhibitors is new and not yet published,” Dr. Atkins and his associates explained.

As of the March 31, 2017, data cutoff, 52 patients from 10 U.S. centers had been treated with the same dose and schedule and were included in the analysis. All patients had tumors with clear cell renal carcinoma histologies; one also had sarcomatoid features.

There were three investigator-assessed dose-limiting toxicities (DLT, the primary endpoint) in the 11 patients treated in the dose-finding phase. One of the patients had a transient ischemic attack and two completed less than 75% of the planned axitinib dose because of treatment-related toxicities.

Of the 52 patients, 25 were still on treatment at the time of data cutoff: 22 who were still receiving both axitinib and pembrolizumab and 3 who were receiving only the PD-1 inhibitor. Eight of the patients continued on therapy despite disease progression.

Of the 27 patients who discontinued both drugs, 10 did so because of adverse events, 9 for disease progression, and others for various reasons such as mixed adverse events and disease progression, investigator discretion, global deterioration, or protocol violation.

Grade 3 or greater adverse events occurred in 34 patients (65%), and included hypertension, diarrhea, fatigue, and elevated alanine aminostransferase (ALT) levels.

The most common potentially immune-related adverse events were diarrhea, ALT elevations, hypothyroidism, and fatigue.

At a median follow-up of 20.4 months, 4 patients had a complete response, and 34 had a partial response. An additional eight patients had stable disease. Responses were seen in 18 of 24 patients with favorable-risk disease and in 18 of 26 patients with intermediate- or poor-risk disease. The median time to response was 2.8 months, and the median duration of response was 18.6 months.
“Future research should focus on investigating the mechanism of the potential synergistic effects of axitinib and pembrolizumab, and whether an immunotherapy-only approach (including combinations) enriched by the appropriate biomarkers, followed by VEGFR TKI salvage, might produce more durable off-treatment responses or whether administering VEGFR TKI monotherapy followed by PD-1 and PD-L1 pathway blockade might produce superior or equivalent results,” the investigators concluded.

Pfizer, in collaboration with Merck, sponsored the study. Dr. Atkins and several coauthors disclosed consulting fees from Pfizer, Merck, and other companies. Four of the coauthors are Pfizer employees and stockholders.

[email protected]

SOURCE: Atkins MB et al. Lancet Oncol 2018 Feb. 10. doi: 10.1016/S1470-2045(18)30081-0.

SAN FRANCISCO – The expression of endogenous retroviruses may be associated with immune checkpoint pathway activation and response to immune checkpoint therapy in clear cell renal cell cancer (ccRCC), according to findings from an analysis of nearly 5,000 tumor samples.

Similar associations may exist in other solid tumors, Shridar Ganesan, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Panda A et al., ASCO-SITC, Abstract #104.

SAN FRANCISCO – The expression of endogenous retroviruses may be associated with immune checkpoint pathway activation and response to immune checkpoint therapy in clear cell renal cell cancer (ccRCC), according to findings from an analysis of nearly 5,000 tumor samples.

Similar associations may exist in other solid tumors, Shridar Ganesan, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Panda A et al., ASCO-SITC, Abstract #104.

SAN FRANCISCO – The expression of endogenous retroviruses may be associated with immune checkpoint pathway activation and response to immune checkpoint therapy in clear cell renal cell cancer (ccRCC), according to findings from an analysis of nearly 5,000 tumor samples.

Similar associations may exist in other solid tumors, Shridar Ganesan, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Sharon Worcester/Frontline Medical News

[email protected]

SOURCE: Panda A et al., ASCO-SITC, Abstract #104.

The combination of the immune checkpoint inhibitor atezolizumab and bevacizumab has efficacy and tolerability superior to that of sunitinib alone as first-line therapy for metastatic renal cell carcinoma, finds the IMmotion151 trial.

“Sunitinib has been the reference standard for this disease for the last 10 years,” lead study author Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium. But strategies using immunotherapy have generated considerable excitement as possible new treatment options.

Findings in context

“This study represents an important breakthrough in kidney cancer therapy,” said Sumanta K. Pal, MD, presscast moderator and ASCO expert. “For several years now, we’ve hosted debates on which treatment strategy is best for this disease, targeted therapy or immune therapy. Now this study, which is really the first of its kind, points to a combination of both as being highly effective in delaying cancer growth and showing an early trend toward improving survival as well.”

It is also noteworthy that the combination has good tolerability that appears better in several respects to that seen with sunitinib, he said. “In my opinion, the side effect profile also compares favorably to what we have seen to date with a dual immunotherapy regimen, namely, nivolumab (Opdivo) and ipilimumab.” Although that combination has also been shown to be more efficacious than sunitinib, nearly 60% of treated patients need steroids for immune-related side effects, compared with only 16% treated with the atezolizumab-bevacizumab combination in IMmotion151.

“I would agree with Dr. Motzer that this data supports consideration of atezolizumab and bevacizumab as a first-line option,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif. “I was intrigued to see that there seemed to be benefit with the combination of atezolizumab and bevacizumab irrespective of the presence or absence of PD-L1.”
 

Study details

About 40% of patients in IMmotion151 had PD-L1–positive tumors. Median investigator-assessed progression-free survival among these patients, a co-primary endpoint, was 11.2 months with atezolizumab-bevacizumab and 7.7 months with sunitinib (hazard ratio, 0.74; P = .02). More modest but still significant benefit was evident among the trial’s entire intention-to-treat population (11.2 vs. 8.4 months; hazard ratio, 0.83; P = .02).

An interim analysis showed that median overall survival among the PD-L1–positive cohort was not reached with atezolizumab-bevacizumab and was 23.3 months with sunitinib (hazard ratio, 0.68; P = .05). Overall survival among the entire trial population, another co-primary endpoint, was not reached in either treatment arm.

The PD-L1–positive cohort had an overall response rate of 43% with atezolizumab-bevacizumab and 35% with sunitinib (complete response rates of 9% and 4%). Corresponding values in the entire trial population were 37% and 33% (5% and 2%).

“Independent review of progression-free survival and response, where the scans are sent off to a committee and they read them blinded to the treatment arm, differed from investigator-assessed outcomes,” Dr. Motzer noted, with lesser benefit from the combination seen in the PD-L1–positive patients. “We are doing further analysis to see if we can identify why there was this difference.”

“One of the main benefits of atezolizumab plus bevacizumab is its safety profile. As an investigator on this study and other studies, I can attest to that: it’s very well tolerated,” he said.

The sunitinib group had higher rates of most treatment-related adverse events, both any grade and grade 3 or worse, especially palmar-plantar erythrodysesthesia, fatigue, and gastrointestinal events. The pattern was similar in the PD-L1–positive subset.

“We also have done an extensive quality of life analysis,” Dr. Motzer said, with some results to be reported at the symposium. “It appears that patients treated with atezolizumab plus bevacizumab have better quality of life compared to sunitinib by a particular scale that assesses trouble with symptoms.”

Dr. Motzer disclosed that he has a consulting or advisory role with Pfizer, Novartis, Eisai, Exelixis, and Merck, and that his institution receives research funding from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Eisai, Novartis, and Genentech/Roche. The study was sponsored by Genentech/Roche.

SOURCE: Motzer RJ et al. GU Cancers Symposium Abstract 578

The combination of the immune checkpoint inhibitor atezolizumab and bevacizumab has efficacy and tolerability superior to that of sunitinib alone as first-line therapy for metastatic renal cell carcinoma, finds the IMmotion151 trial.

“Sunitinib has been the reference standard for this disease for the last 10 years,” lead study author Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium. But strategies using immunotherapy have generated considerable excitement as possible new treatment options.

Findings in context

“This study represents an important breakthrough in kidney cancer therapy,” said Sumanta K. Pal, MD, presscast moderator and ASCO expert. “For several years now, we’ve hosted debates on which treatment strategy is best for this disease, targeted therapy or immune therapy. Now this study, which is really the first of its kind, points to a combination of both as being highly effective in delaying cancer growth and showing an early trend toward improving survival as well.”

It is also noteworthy that the combination has good tolerability that appears better in several respects to that seen with sunitinib, he said. “In my opinion, the side effect profile also compares favorably to what we have seen to date with a dual immunotherapy regimen, namely, nivolumab (Opdivo) and ipilimumab.” Although that combination has also been shown to be more efficacious than sunitinib, nearly 60% of treated patients need steroids for immune-related side effects, compared with only 16% treated with the atezolizumab-bevacizumab combination in IMmotion151.

“I would agree with Dr. Motzer that this data supports consideration of atezolizumab and bevacizumab as a first-line option,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif. “I was intrigued to see that there seemed to be benefit with the combination of atezolizumab and bevacizumab irrespective of the presence or absence of PD-L1.”
 

Study details

About 40% of patients in IMmotion151 had PD-L1–positive tumors. Median investigator-assessed progression-free survival among these patients, a co-primary endpoint, was 11.2 months with atezolizumab-bevacizumab and 7.7 months with sunitinib (hazard ratio, 0.74; P = .02). More modest but still significant benefit was evident among the trial’s entire intention-to-treat population (11.2 vs. 8.4 months; hazard ratio, 0.83; P = .02).

An interim analysis showed that median overall survival among the PD-L1–positive cohort was not reached with atezolizumab-bevacizumab and was 23.3 months with sunitinib (hazard ratio, 0.68; P = .05). Overall survival among the entire trial population, another co-primary endpoint, was not reached in either treatment arm.

The PD-L1–positive cohort had an overall response rate of 43% with atezolizumab-bevacizumab and 35% with sunitinib (complete response rates of 9% and 4%). Corresponding values in the entire trial population were 37% and 33% (5% and 2%).

“Independent review of progression-free survival and response, where the scans are sent off to a committee and they read them blinded to the treatment arm, differed from investigator-assessed outcomes,” Dr. Motzer noted, with lesser benefit from the combination seen in the PD-L1–positive patients. “We are doing further analysis to see if we can identify why there was this difference.”

“One of the main benefits of atezolizumab plus bevacizumab is its safety profile. As an investigator on this study and other studies, I can attest to that: it’s very well tolerated,” he said.

The sunitinib group had higher rates of most treatment-related adverse events, both any grade and grade 3 or worse, especially palmar-plantar erythrodysesthesia, fatigue, and gastrointestinal events. The pattern was similar in the PD-L1–positive subset.

“We also have done an extensive quality of life analysis,” Dr. Motzer said, with some results to be reported at the symposium. “It appears that patients treated with atezolizumab plus bevacizumab have better quality of life compared to sunitinib by a particular scale that assesses trouble with symptoms.”

Dr. Motzer disclosed that he has a consulting or advisory role with Pfizer, Novartis, Eisai, Exelixis, and Merck, and that his institution receives research funding from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Eisai, Novartis, and Genentech/Roche. The study was sponsored by Genentech/Roche.

SOURCE: Motzer RJ et al. GU Cancers Symposium Abstract 578

The combination of the immune checkpoint inhibitor atezolizumab and bevacizumab has efficacy and tolerability superior to that of sunitinib alone as first-line therapy for metastatic renal cell carcinoma, finds the IMmotion151 trial.

“Sunitinib has been the reference standard for this disease for the last 10 years,” lead study author Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium. But strategies using immunotherapy have generated considerable excitement as possible new treatment options.

Findings in context

“This study represents an important breakthrough in kidney cancer therapy,” said Sumanta K. Pal, MD, presscast moderator and ASCO expert. “For several years now, we’ve hosted debates on which treatment strategy is best for this disease, targeted therapy or immune therapy. Now this study, which is really the first of its kind, points to a combination of both as being highly effective in delaying cancer growth and showing an early trend toward improving survival as well.”

It is also noteworthy that the combination has good tolerability that appears better in several respects to that seen with sunitinib, he said. “In my opinion, the side effect profile also compares favorably to what we have seen to date with a dual immunotherapy regimen, namely, nivolumab (Opdivo) and ipilimumab.” Although that combination has also been shown to be more efficacious than sunitinib, nearly 60% of treated patients need steroids for immune-related side effects, compared with only 16% treated with the atezolizumab-bevacizumab combination in IMmotion151.

“I would agree with Dr. Motzer that this data supports consideration of atezolizumab and bevacizumab as a first-line option,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif. “I was intrigued to see that there seemed to be benefit with the combination of atezolizumab and bevacizumab irrespective of the presence or absence of PD-L1.”
 

Study details

About 40% of patients in IMmotion151 had PD-L1–positive tumors. Median investigator-assessed progression-free survival among these patients, a co-primary endpoint, was 11.2 months with atezolizumab-bevacizumab and 7.7 months with sunitinib (hazard ratio, 0.74; P = .02). More modest but still significant benefit was evident among the trial’s entire intention-to-treat population (11.2 vs. 8.4 months; hazard ratio, 0.83; P = .02).

An interim analysis showed that median overall survival among the PD-L1–positive cohort was not reached with atezolizumab-bevacizumab and was 23.3 months with sunitinib (hazard ratio, 0.68; P = .05). Overall survival among the entire trial population, another co-primary endpoint, was not reached in either treatment arm.

The PD-L1–positive cohort had an overall response rate of 43% with atezolizumab-bevacizumab and 35% with sunitinib (complete response rates of 9% and 4%). Corresponding values in the entire trial population were 37% and 33% (5% and 2%).

“Independent review of progression-free survival and response, where the scans are sent off to a committee and they read them blinded to the treatment arm, differed from investigator-assessed outcomes,” Dr. Motzer noted, with lesser benefit from the combination seen in the PD-L1–positive patients. “We are doing further analysis to see if we can identify why there was this difference.”

“One of the main benefits of atezolizumab plus bevacizumab is its safety profile. As an investigator on this study and other studies, I can attest to that: it’s very well tolerated,” he said.

The sunitinib group had higher rates of most treatment-related adverse events, both any grade and grade 3 or worse, especially palmar-plantar erythrodysesthesia, fatigue, and gastrointestinal events. The pattern was similar in the PD-L1–positive subset.

“We also have done an extensive quality of life analysis,” Dr. Motzer said, with some results to be reported at the symposium. “It appears that patients treated with atezolizumab plus bevacizumab have better quality of life compared to sunitinib by a particular scale that assesses trouble with symptoms.”

Dr. Motzer disclosed that he has a consulting or advisory role with Pfizer, Novartis, Eisai, Exelixis, and Merck, and that his institution receives research funding from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Eisai, Novartis, and Genentech/Roche. The study was sponsored by Genentech/Roche.

SOURCE: Motzer RJ et al. GU Cancers Symposium Abstract 578

Retroperitoneal lymphadenectomy (LND) did not improve overall or disease-free survival in fully resected, high-risk, nonmetastatic renal cell carcinoma, according to a secondary analysis of the ASSURE adjuvant trial.

Patients were randomized to adjuvant sorafenib, sunitinib, or placebo in the ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial, and those at high risk – which was defined by cN+ disease or determined at their surgeon’s discretion – underwent LND. The primary objective was to assess the effect of LND on overall survival; secondary objectives included the effect of LND on disease-free survival and the benefit of adjuvant therapy vs. placebo in patients who underwent LND.

Overall, 1,943 patients were enrolled in the ASSURE trial, of which 36.1% (701 patients) underwent LND. A median of three lymph nodes (interquartile range, one to eight) was examined, and disease was pN+ in 23.4% patients. A majority of the patients were male (67.4%), with a median age of 56 years. Most (94.5%) patients underwent radical nephrectomy, and 57.2% patients had open surgery rather than laparoscopic. Tumors were clear cell in 81.7% of cases and Fuhrman grade 3-4 in 66.1%, investigators reported in the Journal Of Urology.

“There was no improvement in overall survival for lymphadenectomy relative to no lymphadenectomy (HR, 1.14; 95% CI, 0.93-1.39; P = .20). For patients who underwent lymphadenectomy with pN+ disease, no improvement in overall or disease-free survival was observed for adjuvant therapy relative to placebo. Lymphadenectomy was overall safe, and did not increase the risk of surgical complications (14.2% vs. 13.4%; P = .63),” wrote Benjamin Ristau, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues. LND was independently associated with other markers of aggressive surgical resection, such as open surgery, radical nephrectomy, and adrenalectomy.

The role of lymphadenectomy in patients undergoing surgery for high-risk renal cell carcinoma remains elusive, the authors wrote. Future strategies include a prospective trial in which patients with high-risk renal cell carcinoma are randomized to specific lymphadenectomy templates.

This study was supported by the National Cancer Institute of National Institutes of Health and the Canadian Cancer Research Institute. Christopher G. Wood reported conflicts of interest with Pfizer, Novartis and Argos. Other authors reported no conflicts of interest.

[email protected]

SOURCE: Ristau BT et al. J Urol. 2018 Jan. doi: 10.1016/j.juro.2017.07.042.

Retroperitoneal lymphadenectomy (LND) did not improve overall or disease-free survival in fully resected, high-risk, nonmetastatic renal cell carcinoma, according to a secondary analysis of the ASSURE adjuvant trial.

Patients were randomized to adjuvant sorafenib, sunitinib, or placebo in the ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial, and those at high risk – which was defined by cN+ disease or determined at their surgeon’s discretion – underwent LND. The primary objective was to assess the effect of LND on overall survival; secondary objectives included the effect of LND on disease-free survival and the benefit of adjuvant therapy vs. placebo in patients who underwent LND.

Overall, 1,943 patients were enrolled in the ASSURE trial, of which 36.1% (701 patients) underwent LND. A median of three lymph nodes (interquartile range, one to eight) was examined, and disease was pN+ in 23.4% patients. A majority of the patients were male (67.4%), with a median age of 56 years. Most (94.5%) patients underwent radical nephrectomy, and 57.2% patients had open surgery rather than laparoscopic. Tumors were clear cell in 81.7% of cases and Fuhrman grade 3-4 in 66.1%, investigators reported in the Journal Of Urology.

“There was no improvement in overall survival for lymphadenectomy relative to no lymphadenectomy (HR, 1.14; 95% CI, 0.93-1.39; P = .20). For patients who underwent lymphadenectomy with pN+ disease, no improvement in overall or disease-free survival was observed for adjuvant therapy relative to placebo. Lymphadenectomy was overall safe, and did not increase the risk of surgical complications (14.2% vs. 13.4%; P = .63),” wrote Benjamin Ristau, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues. LND was independently associated with other markers of aggressive surgical resection, such as open surgery, radical nephrectomy, and adrenalectomy.

The role of lymphadenectomy in patients undergoing surgery for high-risk renal cell carcinoma remains elusive, the authors wrote. Future strategies include a prospective trial in which patients with high-risk renal cell carcinoma are randomized to specific lymphadenectomy templates.

This study was supported by the National Cancer Institute of National Institutes of Health and the Canadian Cancer Research Institute. Christopher G. Wood reported conflicts of interest with Pfizer, Novartis and Argos. Other authors reported no conflicts of interest.

[email protected]

SOURCE: Ristau BT et al. J Urol. 2018 Jan. doi: 10.1016/j.juro.2017.07.042.

Retroperitoneal lymphadenectomy (LND) did not improve overall or disease-free survival in fully resected, high-risk, nonmetastatic renal cell carcinoma, according to a secondary analysis of the ASSURE adjuvant trial.

Patients were randomized to adjuvant sorafenib, sunitinib, or placebo in the ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial, and those at high risk – which was defined by cN+ disease or determined at their surgeon’s discretion – underwent LND. The primary objective was to assess the effect of LND on overall survival; secondary objectives included the effect of LND on disease-free survival and the benefit of adjuvant therapy vs. placebo in patients who underwent LND.

Overall, 1,943 patients were enrolled in the ASSURE trial, of which 36.1% (701 patients) underwent LND. A median of three lymph nodes (interquartile range, one to eight) was examined, and disease was pN+ in 23.4% patients. A majority of the patients were male (67.4%), with a median age of 56 years. Most (94.5%) patients underwent radical nephrectomy, and 57.2% patients had open surgery rather than laparoscopic. Tumors were clear cell in 81.7% of cases and Fuhrman grade 3-4 in 66.1%, investigators reported in the Journal Of Urology.

“There was no improvement in overall survival for lymphadenectomy relative to no lymphadenectomy (HR, 1.14; 95% CI, 0.93-1.39; P = .20). For patients who underwent lymphadenectomy with pN+ disease, no improvement in overall or disease-free survival was observed for adjuvant therapy relative to placebo. Lymphadenectomy was overall safe, and did not increase the risk of surgical complications (14.2% vs. 13.4%; P = .63),” wrote Benjamin Ristau, MD, of Fox Chase Cancer Center in Philadelphia and his colleagues. LND was independently associated with other markers of aggressive surgical resection, such as open surgery, radical nephrectomy, and adrenalectomy.

The role of lymphadenectomy in patients undergoing surgery for high-risk renal cell carcinoma remains elusive, the authors wrote. Future strategies include a prospective trial in which patients with high-risk renal cell carcinoma are randomized to specific lymphadenectomy templates.

This study was supported by the National Cancer Institute of National Institutes of Health and the Canadian Cancer Research Institute. Christopher G. Wood reported conflicts of interest with Pfizer, Novartis and Argos. Other authors reported no conflicts of interest.

[email protected]

SOURCE: Ristau BT et al. J Urol. 2018 Jan. doi: 10.1016/j.juro.2017.07.042.

Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.

Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.

Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.

“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”

This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.

SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.

Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.

Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.

Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.

“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”

This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.

SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.

Overall survival was similar among patients enrolled in clinical trials for metastatic renal cell carcinoma (mRCC) across different geographic regions, according to a pooled retrospective analysis.

Demographic characteristics, clinicopathologic variables, survival, and toxicity data were collected across five geographic regions, including, United States/Canada (USC), Western Europe (WE), Eastern Europe (EE), Latin America (LA), and Asia/Africa/Oceania (AAO) for 4,736 patients who had mRCC treated between 2003 and 2013 and were enrolled in phase 2 and phase 3 clinical trials.

Patients in USC and WE were slightly older (mean ages, 60.6 and 60.5 years, respectively) and with higher numbers undergoing prior nephrectomy. Higher BMI was also observed in patients in the USC and LA regions. While ECOG performance status of 0 was more frequent in LA patients, treatment-related adverse events and use of statin and angiotensin inhibitor system was higher in USC.

“We highlight that, despite different baseline characteristics, OS was similar among patients enrolled in clinical trials across different geographic regions,” reported Andre P. Fay, MD, PhD, and colleagues from Dana Farber Cancer Institute, Boston, in Journal of Global Oncology. “Access to clinical trials may be an important alternative to eliminate health disparities and promote health equity in patients with mRCC.”

This study was supported by Pfizer and in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE, DF/HCC Kidney Cancer Program, and the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. All of the study authors reported disclosures with the sponsor, Pfizer, or other pharmaceutical companies.

SOURCE: Fay AP et al. J Global Oncol. 2018 Jan 17. doi: 10.1200/JGO.17.00119.