First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial

Laurence Albiges; Nizar M. Tannir; Mauricio Burotto; David McDermott; Elizabeth R. Plimack; Philippe Barthélémy; Camillo Porta; Thomas Powles; Frede Donskov; Saby George; Christian K. Kollmannsberger; Howard Gurney; Marc Oliver Grimm; Yoshihiko Tomita; Daniel Castellano; Brian I. Rini; Toni K. Choueiri; David Leung; Shruti Shally Saggi; Chung Wei Lee; M. Brent McHenry; Robert J. Motzer

doi:10.1016/j.eururo.2021.10.001

First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial

Laurence Albiges^*, Nizar M. Tannir, Mauricio Burotto, David McDermott, Elizabeth R. Plimack, Philippe Barthélémy, Camillo Porta, Thomas Powles, Frede Donskov, Saby George, Christian K. Kollmannsberger, Howard Gurney, Marc Oliver Grimm, Yoshihiko Tomita, Daniel Castellano, Brian I. Rini, Toni K. Choueiri, David Leung, Shruti Shally Saggi, Chung Wei LeeM. Brent McHenry, Robert J. Motzer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40–1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. Patient summary: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.

Original language	English
Pages (from-to)	266-271
Number of pages	6
Journal	European Urology
Volume	81
Issue number	3
DOIs	https://doi.org/10.1016/j.eururo.2021.10.001
State	Published - 2021
Externally published	Yes

Bibliographical note

Funding Information:
Financial disclosures: Laurence Albiges certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Laurence Albiges reports consulting fees from Pfizer, Novartis, Bristol Myers Squibb (BMS), Ipsen, Roche, MSD, AstraZeneca, Merck, Amgen, Astellas, and Exelixis; and other fees from Corvus Pharmaceuticals and Peloton Therapeutics. Nizar M. Tannir reports research funding from BMS, Calithera Biosciences, Nektar Therapeutics, Exelixis, Arrowhead Pharmaceuticals, Takeda, and Epizyme, Inc.; and personal fees from BMS, Exelixis, Pfizer, Novartis, Eisai, Lilly Oncology, Neolukin Therapeutics, Ipsen, Nektar Therapeutics, Surface Oncology, Ono Pharmaceutical, and Oncorena. Mauricio Burotto reports consulting/advisory fees from Roche/Genentech, BMS, MSD Oncology, Novartis, and AstraZeneca; and speaker bureau fees from Roche/Genentech, MSD Oncology, BMS, and AstraZeneca. David McDermott reports research funding from BMS, Merck, Genentech/Roche, Novartis, Peloton Therapeutics, Alkermes, and Prometheus Laboratories; consulting/advisory fees from BMS, Merck, Genentech/Roche, Pfizer, Exelixis, Novartis, X4 Pharma, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, and Lilly; and other fees from Beth Israel Deaconess Medical Center. Elizabeth R. Plimack reports institutional research funding from BMS, AstraZeneca, Merck, Peloton Therapeutics, Pfizer, and Astellas; consulting fees from AstraZeneca, BMS, Genentech, Merck, Pfizer, Exelixis, Incyte, Seattle Genetics, Janssen, Flatiron Health, Infinity Pharma, and MEI Pharma; fees for development of educational presentations from BMS and Merck; and US patent application no. 14/588,503. Philippe Barthélémy reports consulting/advisory fees from BMS, Pfizer, MSD Oncology, Novartis, Ipsen, Roche, AstraZeneca, Merck, and Janssen Cilag; travel and accommodation expenses from Amgen; and honoraria from Astellas Pharma. Camillo Porta reports consulting/advisory fees from Angelini Farma, BMS, MSD Oncology, AstraZeneca, Pfizer, Ipsen, Novartis, EUSA Pharma, Eisai, and Merck Serono; speaker fees from Angelini Farma, BMS, MSD Oncology, Pfizer, Ipsen, EUSA Pharma, Eisai, General Electric, Merck Serono, and AstraZeneca; expert testimony fees from Pfizer and EUSA Pharma; and travel and accommodation expenses from Roche. Thomas Powles reports consulting/advisory fees from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, Eisai, and Roche; honoraria from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; institutional research funding from AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; and travel and accommodation expenses from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. Frede Donskov reports institutional research funding from BMS, Pfizer, and Ipsen. Saby George reports consulting/advisory fees from Bayer, BMS, Exelixis, Corvus Pharmaceuticals, Genentech, Sanofi/Genzyme, Pfizer, EMD Serono, Seattle Genetics, Eisai, Merck, QED Therapeutics, and Aveo; and research funding from Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics/Astellas, Calithera Biosciences, Immunomedics, Corvus Pharmaceuticals, and Surface Oncology. Christian K. Kollmannsberger reports advisory board fees from Pfizer, Ipsen, Eisai, Roche, AstraZeneca, and BMS; and honoraria from Pfizer, Ipsen, Eisai, and BMS. Howard Gurney reports advisory board fees from Pfizer, Astellas, Ipsen, Roche, and BMS. Marc-Oliver Grimm reports research funding from BMS and Intuitive Surgical; consulting/advisory fees from AstraZeneca, BMS, Ipsen, MSD, Ono Pharmaceutical, Pfizer, Astellas Pharma, EUSA Pharma, and Merck Serono; honoraria from Astellas Pharma, AstraZeneca, BMS, Medac, MSD, Ono Pharmaceutical, Novartis, Pfizer, Ipsen, Merck Serono, and EUSA Pharma; and travel and accommodation expenses from BMS and Merck Serono. Yoshihiko Tomita reports research funding from Ono Pharmaceutical, Takeda, Astellas, and Chugai; consulting/advisory fees from Ono Pharmaceutical; and honoraria from Ono Pharmaceutical, BMS, and Pfizer. Daniel Castellano reports institutional research funding from Janssen Oncology; consulting/advisory fees from Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, BMS, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, and Boehringher Ingelheim; and travel and accommodation expenses from Pfizer, Roche, BMS, and AstraZeneca Spain. Brian I. Rini reports research funding from Pfizer, Merck, GNE/Roche, Aveo, AstraZeneca, and BMS; consulting fees from BMS, Pfizer, GNE/Roche, Aveo, Novartis, Synthorx, Peloton, Compugen, Merck, Arravive, Surface Oncology, and 3D Medicines; and stock ownership in PTC Therapeutics. Toni K. Choueiri reports consulting/advisory fees from Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Navinata Health, Harborside Press, ASCO, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; travel and accommodation expenses from Pfizer, Bayer, Novartis, GlaxoSmithKilne, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Health, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; international patent application numbers PCT/US2018/058430 and PCT/US2018/12209; honoraria from NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, BMS, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Health, Kidney Cancer Association, Exelixis, Prometheus, LPath, New England Journal of Medicine, Lancet Oncology, Cerulean Pharma, Alligent, EMD Serono, HERON, Lilly, Janssen Oncology, and IQVIA; and institutional research funding from Pfizer, Novartis, Merck, Exelixis, TRACON Pharma, GlaxoSmithKline, BMS, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, and NCI. David Leung is an employee of, owns stock in, has received travel and accommodation expenses from BMS; and reports institutional interest in BMS patents. Shruti Shally Saggi, Chung-Wei Lee, and M. Brent McHenry are employees of and own stock in BMS. Robert J. Motzer reports institutional research funding from Pfizer, Novartis, Eisai, Genentech/Roche, Exelixis, Merck, and BMS; consulting/advisory fees from Pfizer, Novartis, Eisai, Exelixis, Merck, Genentech/Roche, Incyte, Lilly, AstraZeneca, and EMD Serono; and travel and accommodation expenses from BMS.

Funding Information:
Funding/Support and role of the sponsor: This work was supported by Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company (Osaka, Japan). Authors received no financial support or compensation for publication of this manuscript. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672). Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant (Core Grant, number P30 CA008748).

Publisher Copyright:
© 2021 European Association of Urology

Keywords

Advanced renal cell carcinoma
CheckMate 214
Cytoreductive nephrectomy
Ipilimumab
Nivolumab

Access to Document

10.1016/j.eururo.2021.10.001

Cite this

Albiges, L., Tannir, N. M., Burotto, M., McDermott, D., Plimack, E. R., Barthélémy, P., Porta, C., Powles, T., Donskov, F., George, S., Kollmannsberger, C. K., Gurney, H., Grimm, M. O., Tomita, Y., Castellano, D., Rini, B. I., Choueiri, T. K., Leung, D., Saggi, S. S., ... Motzer, R. J. (2021). First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial. European Urology, 81(3), 266-271. https://doi.org/10.1016/j.eururo.2021.10.001

@article{3102f6db082648c68d0ea87192871fce,

title = "First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial",

abstract = "We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40–1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. Patient summary: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.",

keywords = "Advanced renal cell carcinoma, CheckMate 214, Cytoreductive nephrectomy, Ipilimumab, Nivolumab",

author = "Laurence Albiges and Tannir, {Nizar M.} and Mauricio Burotto and David McDermott and Plimack, {Elizabeth R.} and Philippe Barth{\'e}l{\'e}my and Camillo Porta and Thomas Powles and Frede Donskov and Saby George and Kollmannsberger, {Christian K.} and Howard Gurney and Grimm, {Marc Oliver} and Yoshihiko Tomita and Daniel Castellano and Rini, {Brian I.} and Choueiri, {Toni K.} and David Leung and Saggi, {Shruti Shally} and Lee, {Chung Wei} and McHenry, {M. Brent} and Motzer, {Robert J.}",

note = "Funding Information: Financial disclosures: Laurence Albiges certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Laurence Albiges reports consulting fees from Pfizer, Novartis, Bristol Myers Squibb (BMS), Ipsen, Roche, MSD, AstraZeneca, Merck, Amgen, Astellas, and Exelixis; and other fees from Corvus Pharmaceuticals and Peloton Therapeutics. Nizar M. Tannir reports research funding from BMS, Calithera Biosciences, Nektar Therapeutics, Exelixis, Arrowhead Pharmaceuticals, Takeda, and Epizyme, Inc.; and personal fees from BMS, Exelixis, Pfizer, Novartis, Eisai, Lilly Oncology, Neolukin Therapeutics, Ipsen, Nektar Therapeutics, Surface Oncology, Ono Pharmaceutical, and Oncorena. Mauricio Burotto reports consulting/advisory fees from Roche/Genentech, BMS, MSD Oncology, Novartis, and AstraZeneca; and speaker bureau fees from Roche/Genentech, MSD Oncology, BMS, and AstraZeneca. David McDermott reports research funding from BMS, Merck, Genentech/Roche, Novartis, Peloton Therapeutics, Alkermes, and Prometheus Laboratories; consulting/advisory fees from BMS, Merck, Genentech/Roche, Pfizer, Exelixis, Novartis, X4 Pharma, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, and Lilly; and other fees from Beth Israel Deaconess Medical Center. Elizabeth R. Plimack reports institutional research funding from BMS, AstraZeneca, Merck, Peloton Therapeutics, Pfizer, and Astellas; consulting fees from AstraZeneca, BMS, Genentech, Merck, Pfizer, Exelixis, Incyte, Seattle Genetics, Janssen, Flatiron Health, Infinity Pharma, and MEI Pharma; fees for development of educational presentations from BMS and Merck; and US patent application no. 14/588,503. Philippe Barth{\'e}l{\'e}my reports consulting/advisory fees from BMS, Pfizer, MSD Oncology, Novartis, Ipsen, Roche, AstraZeneca, Merck, and Janssen Cilag; travel and accommodation expenses from Amgen; and honoraria from Astellas Pharma. Camillo Porta reports consulting/advisory fees from Angelini Farma, BMS, MSD Oncology, AstraZeneca, Pfizer, Ipsen, Novartis, EUSA Pharma, Eisai, and Merck Serono; speaker fees from Angelini Farma, BMS, MSD Oncology, Pfizer, Ipsen, EUSA Pharma, Eisai, General Electric, Merck Serono, and AstraZeneca; expert testimony fees from Pfizer and EUSA Pharma; and travel and accommodation expenses from Roche. Thomas Powles reports consulting/advisory fees from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, Eisai, and Roche; honoraria from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; institutional research funding from AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; and travel and accommodation expenses from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. Frede Donskov reports institutional research funding from BMS, Pfizer, and Ipsen. Saby George reports consulting/advisory fees from Bayer, BMS, Exelixis, Corvus Pharmaceuticals, Genentech, Sanofi/Genzyme, Pfizer, EMD Serono, Seattle Genetics, Eisai, Merck, QED Therapeutics, and Aveo; and research funding from Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics/Astellas, Calithera Biosciences, Immunomedics, Corvus Pharmaceuticals, and Surface Oncology. Christian K. Kollmannsberger reports advisory board fees from Pfizer, Ipsen, Eisai, Roche, AstraZeneca, and BMS; and honoraria from Pfizer, Ipsen, Eisai, and BMS. Howard Gurney reports advisory board fees from Pfizer, Astellas, Ipsen, Roche, and BMS. Marc-Oliver Grimm reports research funding from BMS and Intuitive Surgical; consulting/advisory fees from AstraZeneca, BMS, Ipsen, MSD, Ono Pharmaceutical, Pfizer, Astellas Pharma, EUSA Pharma, and Merck Serono; honoraria from Astellas Pharma, AstraZeneca, BMS, Medac, MSD, Ono Pharmaceutical, Novartis, Pfizer, Ipsen, Merck Serono, and EUSA Pharma; and travel and accommodation expenses from BMS and Merck Serono. Yoshihiko Tomita reports research funding from Ono Pharmaceutical, Takeda, Astellas, and Chugai; consulting/advisory fees from Ono Pharmaceutical; and honoraria from Ono Pharmaceutical, BMS, and Pfizer. Daniel Castellano reports institutional research funding from Janssen Oncology; consulting/advisory fees from Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, BMS, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, and Boehringher Ingelheim; and travel and accommodation expenses from Pfizer, Roche, BMS, and AstraZeneca Spain. Brian I. Rini reports research funding from Pfizer, Merck, GNE/Roche, Aveo, AstraZeneca, and BMS; consulting fees from BMS, Pfizer, GNE/Roche, Aveo, Novartis, Synthorx, Peloton, Compugen, Merck, Arravive, Surface Oncology, and 3D Medicines; and stock ownership in PTC Therapeutics. Toni K. Choueiri reports consulting/advisory fees from Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Navinata Health, Harborside Press, ASCO, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; travel and accommodation expenses from Pfizer, Bayer, Novartis, GlaxoSmithKilne, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Health, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; international patent application numbers PCT/US2018/058430 and PCT/US2018/12209; honoraria from NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, BMS, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Health, Kidney Cancer Association, Exelixis, Prometheus, LPath, New England Journal of Medicine, Lancet Oncology, Cerulean Pharma, Alligent, EMD Serono, HERON, Lilly, Janssen Oncology, and IQVIA; and institutional research funding from Pfizer, Novartis, Merck, Exelixis, TRACON Pharma, GlaxoSmithKline, BMS, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, and NCI. David Leung is an employee of, owns stock in, has received travel and accommodation expenses from BMS; and reports institutional interest in BMS patents. Shruti Shally Saggi, Chung-Wei Lee, and M. Brent McHenry are employees of and own stock in BMS. Robert J. Motzer reports institutional research funding from Pfizer, Novartis, Eisai, Genentech/Roche, Exelixis, Merck, and BMS; consulting/advisory fees from Pfizer, Novartis, Eisai, Exelixis, Merck, Genentech/Roche, Incyte, Lilly, AstraZeneca, and EMD Serono; and travel and accommodation expenses from BMS. Funding Information: Funding/Support and role of the sponsor: This work was supported by Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company (Osaka, Japan). Authors received no financial support or compensation for publication of this manuscript. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672). Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant (Core Grant, number P30 CA008748). Publisher Copyright: {\textcopyright} 2021 European Association of Urology",

year = "2021",

doi = "10.1016/j.eururo.2021.10.001",

language = "English",

volume = "81",

pages = "266--271",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "3",

}

Albiges, L, Tannir, NM, Burotto, M, McDermott, D, Plimack, ER, Barthélémy, P, Porta, C, Powles, T, Donskov, F, George, S, Kollmannsberger, CK, Gurney, H, Grimm, MO, Tomita, Y, Castellano, D, Rini, BI, Choueiri, TK, Leung, D, Saggi, SS, Lee, CW, McHenry, MB & Motzer, RJ 2021, 'First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial', European Urology, vol. 81, no. 3, pp. 266-271. https://doi.org/10.1016/j.eururo.2021.10.001

TY - JOUR

T1 - First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial

AU - Albiges, Laurence

AU - Tannir, Nizar M.

AU - Burotto, Mauricio

AU - McDermott, David

AU - Plimack, Elizabeth R.

AU - Barthélémy, Philippe

AU - Porta, Camillo

AU - Powles, Thomas

AU - Donskov, Frede

AU - George, Saby

AU - Kollmannsberger, Christian K.

AU - Gurney, Howard

AU - Grimm, Marc Oliver

AU - Tomita, Yoshihiko

AU - Castellano, Daniel

AU - Rini, Brian I.

AU - Choueiri, Toni K.

AU - Leung, David

AU - Saggi, Shruti Shally

AU - Lee, Chung Wei

AU - McHenry, M. Brent

AU - Motzer, Robert J.

N1 - Funding Information: Financial disclosures: Laurence Albiges certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Laurence Albiges reports consulting fees from Pfizer, Novartis, Bristol Myers Squibb (BMS), Ipsen, Roche, MSD, AstraZeneca, Merck, Amgen, Astellas, and Exelixis; and other fees from Corvus Pharmaceuticals and Peloton Therapeutics. Nizar M. Tannir reports research funding from BMS, Calithera Biosciences, Nektar Therapeutics, Exelixis, Arrowhead Pharmaceuticals, Takeda, and Epizyme, Inc.; and personal fees from BMS, Exelixis, Pfizer, Novartis, Eisai, Lilly Oncology, Neolukin Therapeutics, Ipsen, Nektar Therapeutics, Surface Oncology, Ono Pharmaceutical, and Oncorena. Mauricio Burotto reports consulting/advisory fees from Roche/Genentech, BMS, MSD Oncology, Novartis, and AstraZeneca; and speaker bureau fees from Roche/Genentech, MSD Oncology, BMS, and AstraZeneca. David McDermott reports research funding from BMS, Merck, Genentech/Roche, Novartis, Peloton Therapeutics, Alkermes, and Prometheus Laboratories; consulting/advisory fees from BMS, Merck, Genentech/Roche, Pfizer, Exelixis, Novartis, X4 Pharma, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, and Lilly; and other fees from Beth Israel Deaconess Medical Center. Elizabeth R. Plimack reports institutional research funding from BMS, AstraZeneca, Merck, Peloton Therapeutics, Pfizer, and Astellas; consulting fees from AstraZeneca, BMS, Genentech, Merck, Pfizer, Exelixis, Incyte, Seattle Genetics, Janssen, Flatiron Health, Infinity Pharma, and MEI Pharma; fees for development of educational presentations from BMS and Merck; and US patent application no. 14/588,503. Philippe Barthélémy reports consulting/advisory fees from BMS, Pfizer, MSD Oncology, Novartis, Ipsen, Roche, AstraZeneca, Merck, and Janssen Cilag; travel and accommodation expenses from Amgen; and honoraria from Astellas Pharma. Camillo Porta reports consulting/advisory fees from Angelini Farma, BMS, MSD Oncology, AstraZeneca, Pfizer, Ipsen, Novartis, EUSA Pharma, Eisai, and Merck Serono; speaker fees from Angelini Farma, BMS, MSD Oncology, Pfizer, Ipsen, EUSA Pharma, Eisai, General Electric, Merck Serono, and AstraZeneca; expert testimony fees from Pfizer and EUSA Pharma; and travel and accommodation expenses from Roche. Thomas Powles reports consulting/advisory fees from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, Eisai, and Roche; honoraria from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; institutional research funding from AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; and travel and accommodation expenses from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. Frede Donskov reports institutional research funding from BMS, Pfizer, and Ipsen. Saby George reports consulting/advisory fees from Bayer, BMS, Exelixis, Corvus Pharmaceuticals, Genentech, Sanofi/Genzyme, Pfizer, EMD Serono, Seattle Genetics, Eisai, Merck, QED Therapeutics, and Aveo; and research funding from Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics/Astellas, Calithera Biosciences, Immunomedics, Corvus Pharmaceuticals, and Surface Oncology. Christian K. Kollmannsberger reports advisory board fees from Pfizer, Ipsen, Eisai, Roche, AstraZeneca, and BMS; and honoraria from Pfizer, Ipsen, Eisai, and BMS. Howard Gurney reports advisory board fees from Pfizer, Astellas, Ipsen, Roche, and BMS. Marc-Oliver Grimm reports research funding from BMS and Intuitive Surgical; consulting/advisory fees from AstraZeneca, BMS, Ipsen, MSD, Ono Pharmaceutical, Pfizer, Astellas Pharma, EUSA Pharma, and Merck Serono; honoraria from Astellas Pharma, AstraZeneca, BMS, Medac, MSD, Ono Pharmaceutical, Novartis, Pfizer, Ipsen, Merck Serono, and EUSA Pharma; and travel and accommodation expenses from BMS and Merck Serono. Yoshihiko Tomita reports research funding from Ono Pharmaceutical, Takeda, Astellas, and Chugai; consulting/advisory fees from Ono Pharmaceutical; and honoraria from Ono Pharmaceutical, BMS, and Pfizer. Daniel Castellano reports institutional research funding from Janssen Oncology; consulting/advisory fees from Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, BMS, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, and Boehringher Ingelheim; and travel and accommodation expenses from Pfizer, Roche, BMS, and AstraZeneca Spain. Brian I. Rini reports research funding from Pfizer, Merck, GNE/Roche, Aveo, AstraZeneca, and BMS; consulting fees from BMS, Pfizer, GNE/Roche, Aveo, Novartis, Synthorx, Peloton, Compugen, Merck, Arravive, Surface Oncology, and 3D Medicines; and stock ownership in PTC Therapeutics. Toni K. Choueiri reports consulting/advisory fees from Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Navinata Health, Harborside Press, ASCO, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; travel and accommodation expenses from Pfizer, Bayer, Novartis, GlaxoSmithKilne, Merck, BMS, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, Alligent, Ipsen, Corvus Pharmaceuticals, LPath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Association, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Health, The New England Journal of Medicine, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO; international patent application numbers PCT/US2018/058430 and PCT/US2018/12209; honoraria from NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, BMS, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Health, Kidney Cancer Association, Exelixis, Prometheus, LPath, New England Journal of Medicine, Lancet Oncology, Cerulean Pharma, Alligent, EMD Serono, HERON, Lilly, Janssen Oncology, and IQVIA; and institutional research funding from Pfizer, Novartis, Merck, Exelixis, TRACON Pharma, GlaxoSmithKline, BMS, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, and NCI. David Leung is an employee of, owns stock in, has received travel and accommodation expenses from BMS; and reports institutional interest in BMS patents. Shruti Shally Saggi, Chung-Wei Lee, and M. Brent McHenry are employees of and own stock in BMS. Robert J. Motzer reports institutional research funding from Pfizer, Novartis, Eisai, Genentech/Roche, Exelixis, Merck, and BMS; consulting/advisory fees from Pfizer, Novartis, Eisai, Exelixis, Merck, Genentech/Roche, Incyte, Lilly, AstraZeneca, and EMD Serono; and travel and accommodation expenses from BMS. Funding Information: Funding/Support and role of the sponsor: This work was supported by Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company (Osaka, Japan). Authors received no financial support or compensation for publication of this manuscript. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672). Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant (Core Grant, number P30 CA008748). Publisher Copyright: © 2021 European Association of Urology

PY - 2021

Y1 - 2021

N2 - We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40–1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. Patient summary: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.

AB - We present an exploratory post hoc analysis from the phase 3 CheckMate 214 trial of first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) without prior nephrectomy and with an evaluable primary tumor, a population under-represented in clinical trials. Patients with clear cell aRCC were randomized to NIVO+IPI every 3 wk for four doses followed by NIVO monotherapy, or sunitinib every day for 4 wk (6-wk cycle). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and primary tumor shrinkage were assessed. PFS and ORR were assessed per independent radiology review committee using RECIST version 1.1. With minimum study follow-up of 4 yr for intent-to-treat patients, OS favored NIVO+IPI (n = 53) over sunitinib (n = 55; hazard ratio 0.63, 95% confidence interval 0.40–1.0) among patients without prior nephrectomy. ORR was higher (34% vs 15%; p = 0.0041) and median duration of response was longer with NIVO+IPI versus sunitinib (20.5 vs 14.1 mo); the best overall response was partial response in either arm. A ≥30% reduction in the diameter of intact target renal tumors was achieved in 35% of patients with NIVO+IPI versus 20% with sunitinib. Safety was consistent with the global study population. In conclusion, in patients with aRCC without prior nephrectomy and with an evaluable primary tumor, NIVO+IPI showed survival benefits and renal tumor reduction versus sunitinib. This trial is registered at ClinicalTrials.gov as NCT02231749. Patient summary: In an exploratory analysis of a large global trial (CheckMate 214), we observed positive outcomes (both survival and tumor response to treatment) with nivolumab plus ipilimumab over sunitinib in a subgroup of patients with advanced kidney cancer who did not undergo removal of their primary kidney tumor. This subset of patients represents a population that has not been studied in clinical trials and for whom outcomes with new immunotherapy combination regimens are not yet known. We conclude that treatment with nivolumab plus ipilimumab offers these patients a survival benefit versus sunitinib, consistent with that observed in the overall study, as well as a notable kidney tumor reduction.

KW - Advanced renal cell carcinoma

KW - CheckMate 214

KW - Cytoreductive nephrectomy

KW - Ipilimumab

KW - Nivolumab

UR - http://www.scopus.com/inward/record.url?scp=85118750007&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/07af65b6-3107-3769-aa20-fcc3e98896db/

U2 - 10.1016/j.eururo.2021.10.001

DO - 10.1016/j.eururo.2021.10.001

M3 - Article

AN - SCOPUS:85118750007

SN - 0302-2838

VL - 81

SP - 266

EP - 271

JO - European Urology

JF - European Urology

IS - 3

ER -

First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial

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