Abstract
Background: The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively. Objective: To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC. Design, setting, and participants: IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab. Intervention: Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy. Outcome measurements and statistical analysis: The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods. Results and limitations: Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors. Conclusions: The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. Patient summary: Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable. Patients with metastatic renal clear cell carcinoma whose disease progressed on atezolizumab or sunitinib monotherapy were treated with atezolizumab plus bevacizumab. Anti–vascular endothelial growth factor (VEGF) therapy with cancer immunotherapy demonstrated efficacy after failure of immune checkpoint or VEGF receptor inhibitor therapy.
Original language | English (US) |
---|---|
Journal | European urology |
DOIs | |
State | Accepted/In press - 2021 |
Keywords
- Atezolizumab
- Bevacizumab
- Cancer immunotherapy
- Metastatic
- Renal cell carcinoma
- Second line
- Sunitinib
- Vascular endothelial growth factor inhibitor
ASJC Scopus subject areas
- Urology
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Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150 : A Randomized Phase 2 Clinical Trial. / Powles, Thomas; Atkins, Michael B.; Escudier, Bernard; Motzer, Robert J.; Rini, Brian I.; Fong, Lawrence; Joseph, Richard W.; Pal, Sumanta K.; Sznol, Mario; Hainsworth, John; Stadler, Walter M.; Hutson, Thomas E.; Ravaud, Alain; Bracarda, Sergio; Suarez, Cristina; Choueiri, Toni K.; Reeves, James; Cohn, Allen; Ding, Beiying; Leng, Ning; Hashimoto, Kenji; Huseni, Mahrukh; Schiff, Christina; McDermott, David F.
In: European urology, 2021.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150
T2 - A Randomized Phase 2 Clinical Trial
AU - Powles, Thomas
AU - Atkins, Michael B.
AU - Escudier, Bernard
AU - Motzer, Robert J.
AU - Rini, Brian I.
AU - Fong, Lawrence
AU - Joseph, Richard W.
AU - Pal, Sumanta K.
AU - Sznol, Mario
AU - Hainsworth, John
AU - Stadler, Walter M.
AU - Hutson, Thomas E.
AU - Ravaud, Alain
AU - Bracarda, Sergio
AU - Suarez, Cristina
AU - Choueiri, Toni K.
AU - Reeves, James
AU - Cohn, Allen
AU - Ding, Beiying
AU - Leng, Ning
AU - Hashimoto, Kenji
AU - Huseni, Mahrukh
AU - Schiff, Christina
AU - McDermott, David F.
N1 - Funding Information: Funding/Support and role of the sponsor: This study was sponsored by F. Hoffmann-La Roche Ltd . Authors were funded by National Cancer Institute grants P50 CA101942 to Drs. David F. McDermott and Toni K. Choueiri, P30 CA008748 to Dr. Robert J. Motzer, and P30 CA14599 to Dr. Walter M. Stadler. F. Hoffmann-La Roche Ltd. was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: Financial disclosures: Thomas Powles 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: All authors report funding of editorial support from F. Hoffmann-La Roche, Ltd. Thomas Powles has received research funding from AstraZeneca and Roche; and honoraria from AstraZeneca, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Exelixis, and Merck Sharp & Dohme. Michael B. Atkins has received honoraria or fees for serving on advisory boards for Bristol-Meyers Squibb (BMS), Merck, Novartis, Arrowhead, Pfizer, Galactone, Werewolf, Fathom, Pneuma, and Leads; has received consulting fees from BMS, Merck, Novartis, Pfizer, Genentech/Roche, Exelixis, Eisai, Aveo, Array, AstraZeneca, Idera, Aduro, ImmunoCore, Boehringer Ingelheim, Iovance, Newlink Pharma, Surface, Alexion, Acceleron, Cota, and Amgen; has received institutional support from BMS, Merck, Pfizer, and Genentech; and owns stock options in Werewolf and Pyxis Oncology. Bernard Escudier has received grants from Aveo, BMS, and Novartis; and personal fees from BMS, Roche, Pfizer, Oncorena, Aveo, and Ipsen. Robert J. Motzer has received honoraria for consulting roles from Bristol-Myers Squibb, Roche-Genentech, Pfizer, Novartis, Exelixis, Eisai, Incyte, Eli Lilly, and Merck; and institutional support from Bristol-Myers Squibb, Roche/Genentech, Pfizer, Novartis, Exelixis, and Eisai. Brian I. Rini has received grants and honoraria from Roche/Genentech and Pfizer; has received grants to his institution and honoraria for consulting roles from Merck, Peloton, Aveo, BMS; has received grants to his institution from AstraZeneca; has received honoraria for consulting roles from Novartis, Synthorx, Compugen, Corvus, and Exelixis; and owns stock in PTC therapeutics. Richard W. Joseph has received honoraria for serving on advisory boards for BMS, Array, and Exelixis. Sumanta K. Pal has received consulting fees from Roche/Genentech, Aveo, Eisai, Pfizer, Novartis, Exelixis, Ipsen, BMS, and Astellas. Mario Sznol has received consulting fees from Genentech/Roche, BMS, AstraZeneca/MedImmune, Pfizer, Novartis, Kyowa Kirin, Seattle Genetics, Nektar, Pierre Fabre, Lilly, Merck US, Theravance, Biodesix, Vaccinex, Janssen/Johnson & Johnson, Modulate Therapies, Baxalta-Shire, Incyte, NewLink Genetics, Iovance, AgonOx, Arbutus, Celldex, Inovio, Gritsone, Molecular Partners, Innate Pharma, AbbVie, Immunocore, Genmab, Almac, Hinge, Allakos, Anaeropharma, Array, GI Innovation, Genocea, and Chugai-Roche; has received fees for serving on advisory boards for Symphogen, Adaptimmune, Omniox, Pieris, and Torque, and formerly for Lycera; and owns stock options in Torque, Amphivena, Adaptive Biotechnologies, Intensity, and Actym. John Hainsworth has received institutional support from Roche/Genentech for participation in a clinical trial. Walter M. Stadler has received consulting fees from AstraZeneca, Bayer, BMS, Caremark/CVS, Clovis, Eisai, Genentech, Merck, Pfizer, and Sotio; has received institutional support from AbbVie, AstraZeneca, Astellas/Medivation, Bayer, BMS, Boehringer Ingelheim, Calithera, Clovis, Eisai, Exelixis, Genentech/Roche, Johnson & Johnson/Janssen, Merck, Novartis, Pfizer, Seattle Genetics, Tesaro, and X4 Pharmaceuticals; has served on the speaker bureau of the following CME providers (sponsorship unknown): Applied Clinical Education, Dava Oncology, Global Academy for Medical Education, OncLive, PeerView, Vindico; and serves as an editor for Cancer and UpToDate. Thomas E. Hutson has received honoraria or fees for serving on advisory boards, has received honoraria or fees for consulting roles, has received research support, and served on the speaker bureau for Pfizer, BMS, Janssen, Astellas, EMD Serono, Aveo, Exelixis, Merck, and Novartis. Alain Ravaud has received fees and nonfinancial support from Pfizer, AstraZeneca, BMS, Ipsen, Roche, and Novartis; and institutional support from Pfizer. Sergio Bracarda has received honoraria and travel support for advisory roles from Novartis, Astellas, Janssen, Pfizer, BMS, Roche, and Ipsen; honoraria from Merck Sharp & Dohme, and travel support from Exelixis. Cristina Suárez has received grants from Roche for conduct of the study; advisory board, and speaking and travel fees from BMS and Pfizer; advisory board and speaking fees from Ipsen and Astellas; advisory board fees from Sanofi, Bayer, and Merck Sharp & Dohme; and travel expenses from Roche. Toni K. Choueiri has received institutional support, grants, fees for consulting and advisory boards, and travel and accommodations from Pfizer, Exelixis AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Prometheus Labs, Corvus, and Ipsen; has received institutional and research support from Tracon; has received consulting and advisory board fees and travel and accommodations from Allegiant, UpToDate, NCCN, Analysis Group, Michael J. Hennessy Associates, Inc, OncLive, PER, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, NEJM, and Lancet Oncology; has received research and institutional support from Calithera and Takeda; and holds patents related to two pending and issued patents on biomarkers predictive of immune checkpoint response. James Reeves has received institutional support from the Sarah Cannon Research Institute, Eli Lilly, Tesaro, TG Therapeutics, Genentech, Celgene, Merck, BMS, Boston Biomedical Inc, AstraZeneca, Novocure, Calithera Biosciences, Novartis, Guardant Health, Acerta Pharma, Rhizen Pharmaceuticals, Takeda Pharmaceuticals, Onconova Therapeutics, Sanofi, and CTI Biopharma; and received speaking fees and travel support from Eisai and Janssen. Allen Cohn has received speaking fees from BMS and Ipsen. Beiying Ding and Kenji Hashimoto are employees and stockholders of Roche. Mahrukh Huseni and Ning Leng are employees and hold stock options in Roche/Genentech. Christina Schiff was previously employed and previously owned stock options in Roche/Genentech. David F. McDermott has received consulting fees from BMS, Pfizer, Merck, Novartis, Array BioPharma, Eli Lilly, EMD Serono, Jounce Therapeutics, Peloton, and Alkermes; and research grants from Prometheus Laboratories and BMS. Funding Information: Acknowledgments: The authors would like to acknowledge Jiaheng Qiu and Cindy (Qian) Zhu at Genentech, Inc., for contributions to data analyses. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Medical writing assistance for this manuscript was provided by Christopher Lum, PhD, of Health Interactions, Inc., and funded by F. Hoffmann-La Roche, Ltd. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively. Objective: To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC. Design, setting, and participants: IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab. Intervention: Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy. Outcome measurements and statistical analysis: The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods. Results and limitations: Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors. Conclusions: The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. Patient summary: Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable. Patients with metastatic renal clear cell carcinoma whose disease progressed on atezolizumab or sunitinib monotherapy were treated with atezolizumab plus bevacizumab. Anti–vascular endothelial growth factor (VEGF) therapy with cancer immunotherapy demonstrated efficacy after failure of immune checkpoint or VEGF receptor inhibitor therapy.
AB - Background: The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively. Objective: To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC. Design, setting, and participants: IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab. Intervention: Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy. Outcome measurements and statistical analysis: The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods. Results and limitations: Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors. Conclusions: The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. Patient summary: Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable. Patients with metastatic renal clear cell carcinoma whose disease progressed on atezolizumab or sunitinib monotherapy were treated with atezolizumab plus bevacizumab. Anti–vascular endothelial growth factor (VEGF) therapy with cancer immunotherapy demonstrated efficacy after failure of immune checkpoint or VEGF receptor inhibitor therapy.
KW - Atezolizumab
KW - Bevacizumab
KW - Cancer immunotherapy
KW - Metastatic
KW - Renal cell carcinoma
KW - Second line
KW - Sunitinib
KW - Vascular endothelial growth factor inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85101408182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101408182&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2021.01.003
DO - 10.1016/j.eururo.2021.01.003
M3 - Article
AN - SCOPUS:85101408182
JO - European Urology
JF - European Urology
SN - 0302-2838
ER -