TY - JOUR
T1 - Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies
AU - McGregor, Bradley Alexander
AU - Campbell, Matthew
AU - Xie, Wanling
AU - Farah, Subrina
AU - Bilen, Mehmet A.
AU - Schmidt, Andrew L.
AU - Sonpavde, Guru P.
AU - Kilbridge, Kerry L.
AU - Choudhury, Atish D.
AU - Mortazavi, Amir
AU - Shah, Amishi Y.
AU - Venkatesan, Aradhana M.
AU - Bubley, Glenn J.
AU - Siefker-Radtke, Arlene O.
AU - McKay, Rana R.
AU - Choueiri, Toni K.
N1 - Funding Information:
This work was supported by Bristol‐Myers Squibb. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672).
Funding Information:
Bradley Alexander McGregor discloses payment for consulting from Bayer, Astellas, AstraZeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech, Eisai, and EMD Serono and personal fees from Dendreon and Bristol‐Myers Squibb and has received research support for the Dana‐Farber Cancer Institute from Bristol‐Myers Squibb, Calithera, Exelixis, and Seattle Genetics. Matthew T. Campbell discloses payment for consulting/advisory boards from Apricity Health, Astellas, Exelixis, AstraZeneca, Eisai, EMD Serono, Genentech, Seattle Genetics, and Pfizer; reports sponsored education programs by Bristol‐Myers Squibb, Roche, and AstraZeneca; has performed education programs (not continuing medical education) for Roche and Pfizer/EMD Serono; and has received support for research from Exelixis, Janssen, AstraZeneca, Pfizer/EMD Serono, and Apricity Health. Mehmet A. Bilen has acted as a paid consultant for and/or as a member of advisory boards for Exelixis, Bayer, Bristol‐Myers Squibb, Eisai, Pfizer, AstraZeneca, Janssen, Genomic Health, Nektar, and Sanofi and has received grants for his institution from Xencor, Bayer, Bristol‐Myers Squibb, Genentech/Roche, Seattle Genetics, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peleton Therapeutics, and Pfizer for work performed outside the submitted work. Andrew L. Schmidt has received educational travel assistance from Astellas and Pfizer. Guru P. Sonpavde discloses payment for consulting from Dava Oncology, Pfizer, Bristol‐Myers Squibb, Genentech, EMD Serono, Novartis, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Amgen, Eisai, and Bicycle Therapeutics; personal fees from UpToDate, Physicians Education Resource, OncLive, Research to Practice, Medscape, and Elsevier Practice Update; grants from Janssen; research support for his institution from Boehringer‐Ingelheim, Bayer, Pfizer, Merck, Sanofi, and AstraZeneca; and travel fees from Bristol‐Myers Squibb and AstraZeneca. He is also on steering committees for trials for Bristol‐Myers Squibb, Bavarian Nordic, Seattle Genetics, and QED (all unpaid) and AstraZeneca and Debiopharm (both paid). Atish D. Choudhury discloses honoraria from Clovis, Dendreon, and Bayer and research funding for his institution from Bayer and Pfizer. Amir Mortazavi serves on advisory boards for Seattle Genetics and Pfizer and on a scientific advisory board for Debiopharm Group; he has received research funding for his institution from Acerta Pharma, Genentech, Roche, Merck, Novartis, Seattle Genetics, Astellas Pharma, Mirati Therapeutics, Bristol‐Myers Squibb, and Debiopharm Group. Amishi Y. Shah discloses payment for consulting from Eisai, Oncology Information Group/Roche, Pfizer, and Exelixis; personal fees from Bristol‐Myers Squibb; and research support from Bristol‐Myers Squibb, Eisai, and EMD Serono. Aradhana M. Venkatesan reports consulting for Pfizer; research support from the National Institutes of Health/National Cancer Institute (award P30 CA016672); awards from the Institutional Research Grant Program and the Radiation Oncology and Cancer Imaging Program of The University of Texas MD Anderson Cancer Center; and grants from Toshiba America Medical Systems and the Radiological Society for North America. Arlene O. Siefker‐Radtke has served on advisory boards for AstraZeneca, Bavarian Nordic, Genentech, Janssen, Merck, Mirati, Nektar Therapeutics, and Seattle Genetics; has received research funding through her institution from Basilea Pharmaceutica, Bristol‐Myers Squibb, Janssen, Merck, Millennium, Mirati, and Nektar Therapeutics; and is a speaker for Janssen. Rana R. McKay has received research funding from Bayer, Pfizer, and Tempus; serves on advisory boards for Bayer, Bristol‐Myers Squib, Exelixis, Janssen, Novartis, Pfizer, Sanofi, Tempus, and Merck; and is a consultant for Dendreon and Vividion. Toni K. Choueiri reports grants and personal fees from AstraZeneca, Bristol‐Myers Squibb, Eisai, GlaxoSmithKline, Merck, Exelixis, Genentech, and Corvus; personal fees from Bayer, Cerulean, Foundation Medicine, Roche, Prometheus Labs, and Ipsen; and grants from Pfizer, Novartis, Peloton, EMD Serono, Lilly, Risai, Tracon, and Astellas outside the submitted work. The other authors made no disclosures.
PY - 2021/3/15
Y1 - 2021/3/15
N2 - Background: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). Methods: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). Results: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.
AB - Background: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). Methods: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). Results: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.
KW - adrenal tumor
KW - bladder or upper tract tumor of variant histology
KW - genitourinary
KW - immunotherapy
KW - rare cancer
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U2 - 10.1002/cncr.33328
DO - 10.1002/cncr.33328
M3 - Article
C2 - 33216356
AN - SCOPUS:85096641370
SN - 0008-543X
VL - 127
SP - 840
EP - 849
JO - Cancer
JF - Cancer
IS - 6
ER -