PMID- 35397432 OWN - NLM STAT- MEDLINE DCOM- 20220503 LR - 20220716 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 7 IP - 2 DP - 2022 Apr TI - Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101. PG - 100450 LID - S2059-7029(22)00066-7 [pii] LID - 10.1016/j.esmoop.2022.100450 [doi] LID - 100450 AB - BACKGROUND: In the phase III JAVELIN Renal 101 trial, first-line avelumab plus axitinib demonstrated a progression-free survival (PFS) and objective response rate (ORR) benefit versus sunitinib in patients with advanced renal cell carcinoma (aRCC). However, efficacy in elderly patients remains unclear. We report efficacy and safety by age group from the second interim analysis of overall survival (OS). PATIENTS AND METHODS: PFS and ORR as per blinded independent central review (RECIST 1.1), OS, and safety were assessed in patient groups aged <65, >/=65 to <75, and >/=75 years. RESULTS: In the avelumab plus axitinib and sunitinib arms, 271/138/33 and 275/128/41 patients aged <65, >/=65 to <75, and >/=75 years, respectively, were randomized. At data cut-off (January 2019), median PFS [95% confidence interval (CI)] with avelumab plus axitinib versus sunitinib in these respective age groups was 11.6 (8.4-19.4) versus 6.9 (5.6-8.4) months [hazard ratio (HR), 0.63; 95% CI 0.501-0.786], 13.8 (11.1-18.0) versus 11.0 (7.8-16.6) months (HR, 0.88; 95% CI 0.627-1.231), and 13.8 [7.0-not estimable (NE)] versus 9.8 (4.3-NE) months (HR, 0.76; 95% CI 0.378-1.511). Median OS (95% CI) in the respective age groups was not reached (NR) (NE-NE) versus 28.6 (25.5-NE) months (HR, 0.74; 95% CI 0.541-1.022), 30.0 (30.0-NE) versus NR (NE-NE) months (HR, 0.89; 95% CI 0.546-1.467), and 25.3 (19.9-NE) versus NR (19.4-NE) months (HR, 0.87; 95% CI 0.359-2.106). ORR (95% CI) in the respective age groups was 49.4% (43.3% to 55.6%) versus 27.3% (22.1% to 32.9%), 60.9% (52.2% to 69.1%) versus 28.9% (21.2% to 37.6%), and 42.4% (25.5% to 60.8%) versus 22.0% (10.6% to 37.6%). In the avelumab plus axitinib arm, grade >/=3 adverse events (AEs) and immune-related AEs occurred in 76.9%/81.2%/72.7% and 45.5%/48.1%/36.4% in the respective age groups. CONCLUSIONS: First-line avelumab plus axitinib demonstrated favorable efficacy across age groups, including patients aged >/=75 years. OS data were still immature; follow-up is ongoing. The safety profile was generally consistent across age groups. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Tomita, Y AU - Tomita Y AD - Department of Urology, Niigata University Graduate School of Medicine, Niigata, Japan; Department of Molecular Oncology, Niigata University Graduate School of Medicine, Niigata, Japan. Electronic address: ytomita@med.niigata-u.ac.jp. FAU - Motzer, R J AU - Motzer RJ AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. FAU - Choueiri, T K AU - Choueiri TK AD - The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, USA. FAU - Rini, B I AU - Rini BI AD - Department of Hematology and Medical Oncology, Vanderbilt University, Nashville, USA. FAU - Miyake, H AU - Miyake H AD - Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Uemura, H AU - Uemura H AD - Department of Urology, Faculty of Medicine, Kindai University, Osaka, Japan. FAU - Albiges, L AU - Albiges L AD - Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France. FAU - Fujii, Y AU - Fujii Y AD - Pfizer R&D Japan, Tokyo, Japan. FAU - Umeyama, Y AU - Umeyama Y AD - Pfizer R&D Japan, Tokyo, Japan. FAU - Wang, J AU - Wang J AD - Pfizer, Cambridge, USA. FAU - Mariani, M AU - Mariani M AD - Pfizer srl, Milan, Italy. FAU - Schmidinger, M AU - Schmidinger M AD - Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220406 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 RN - 0 (Antibodies, Monoclonal, Humanized) RN - C9LVQ0YUXG (Axitinib) RN - KXG2PJ551I (avelumab) RN - V99T50803M (Sunitinib) SB - IM MH - Aged MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Axitinib/adverse effects MH - *Carcinoma, Renal Cell/drug therapy MH - Female MH - Follow-Up Studies MH - Humans MH - *Kidney Neoplasms/drug therapy/pathology MH - Male MH - Sunitinib/adverse effects PMC - PMC9058903 OTO - NOTNLM OT - avelumab plus axitinib OT - elderly OT - immune checkpoint inhibitor OT - phase III OT - renal cell carcinoma COIS- Disclosure YT has received honoraria from Pfizer, Astellas Pharma, Novartis, Ono Pharmaceutical, Bristol Myers Squibb, and Chugai Pharma; has served in a consulting or advisory role for Novartis, Ono Pharmaceutical, and Taiho Pharmaceutical; and has received research funding paid to his institution from Pfizer, Ono Pharmaceutical, Takeda, Astellas Pharma, AstraZeneca, Novartis, Chugai Pharma, MSD, and Eisai. RJM has served in a consulting or advisory role for AstraZeneca, Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, Genentech/Roche, Incyte, Lilly, MSD, Novartis, and Pfizer; has received research funding paid to his institution, from Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, MSD, Novartis, and Pfizer; and has received travel, accommodations, and expenses from Bristol Myers Squibb. TKC owns stock and additional ownership interests in Pionyr and Tempest Therapeutics; has received honoraria from Alexion Pharmaceuticals, Alligent, Analysis Group, ASCO, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, MSD, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Sanofi/Aventis, New England Journal of Medicine, and UpToDate; has served in a consulting or advisory role for Alexion Pharmaceuticals, Alligent, Analysis Group, ASCO, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, ESMO, Exelixis, Foundation Medicine, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, MSD, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Roche/Genentech, Sanofi/Aventis, New England Journal of Medicine, and UpToDate; has received research funding paid to his institution, from Agensys, Analysis Group, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Celldex, Cerulean Pharma, Congressionally Directed Medical Research Programs (DOD), Corvus Pharmaceuticals, Eisai, Exelixis, Foundation Medicine, Gateway for Cancer Research, GlaxoSmithKline, Ipsen, MSD, NCI, Novartis, Peloton Therapeutics, Pfizer, Prometheus, Roche, Roche/Genentech, Seattle Genetics/Astellas, Takeda, and TRACON Pharmaceuticals; owns patents, royalties, or other intellectual property for international patent application no. PCT/US2018/058430, entitled 'Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy' and international patent application no. PCT/US2018/12209, entitled 'PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response'; and has received travel, accommodations, and expenses from Alexion Pharmaceuticals, Alligent, Analysis Group, AstraZeneca, Bayer, Bristol Myers Squibb, Cerulean Pharma, Clinical Care Options, Corvus Pharmaceuticals, Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, ESMO, Exelixis, Foundation Medicine, GlaxoSmithKline, Harborside Press, HERON, Ipsen, Kidney Cancer Association, Lancet Oncology, Lilly, Lpath, MSD, Michael J. Hennessy Associates, Navinata Health, NCCN, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus, Roche/Genentech, Sanofi/Aventis, New England Journal of Medicine, and UpToDate. BIR owns stock and other ownership interests in PTC Therapeutics; has served in a consulting or advisory role for Bristol Myers Squibb, Pfizer, Genentech/Roche, Aveo, Synthorx, Compugen, MSD, Corvus, Surface Oncology, 3D Medicines, Aravive, Alkermes, Arrowhead, GSK, and Shionogi; has received research funding paid to his institution, from Pfizer, MSD, Genentech/Roche, Aveo, AstraZeneca, Bristol Myers Squibb, and Exelixis; and has received travel, accommodations, and expenses from MSD, Pfizer, and Bristol Myers Squibb. HM has received honoraria; served in a consulting or advisory role for; and has received research funding paid to his institution from Pfizer. HU has received speakers' bureau fees from Pfizer, Bayer, MSD, Bristol Myers Squibb, and Janssen; and has received research funding paid to his institution from Takeda, Daiichi Sankyo, Astellas Pharma, Ono Pharmaceutical, AstraZeneca, Sanofi, and Kissei Pharmaceutical. LA has served in a consulting or advisory role for Amgen, Bristol Myers Squibb, Ipsen, Roche, Novartis, Pfizer, Astellas Pharma, Merck, MSD, AstraZeneca, Exelixis, Corvus, Peloton Therapeutics, Exelixis, and Janssen; has received research funding paid to her institution, from Bristol Myers Squibb; and has received travel, accommodations, and expenses from Bristol Myers Squibb and MSD. YF is an employee of Pfizer R&D Japan. YU is an employee of Pfizer R&D Japan and owns stock in Pfizer. JW is an employee of Pfizer and owns stock in Pfizer. MM is an employee of Pfizer. MS has received honoraria from Pfizer, Merck, Bristol Myers Squibb, MSD, Ipsen, Exelixis, Eisai, EUSA, and Alkermes; has served in a consulting or advisory role for Pfizer, Merck, Bristol Myers Squibb, MSD, Ipsen, Exelixis, Eisai, EUSA, and Alkermes; and has received travel, accommodations, and expenses from Pfizer, Roche, and Ipsen. Data sharing Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. EDAT- 2022/04/10 06:00 MHDA- 2022/05/04 06:00 PMCR- 2022/04/06 CRDT- 2022/04/09 20:11 PHST- 2021/11/02 00:00 [received] PHST- 2022/02/06 00:00 [revised] PHST- 2022/02/16 00:00 [accepted] PHST- 2022/04/10 06:00 [pubmed] PHST- 2022/05/04 06:00 [medline] PHST- 2022/04/09 20:11 [entrez] PHST- 2022/04/06 00:00 [pmc-release] AID - S2059-7029(22)00066-7 [pii] AID - 100450 [pii] AID - 10.1016/j.esmoop.2022.100450 [doi] PST - ppublish SO - ESMO Open. 2022 Apr;7(2):100450. doi: 10.1016/j.esmoop.2022.100450. Epub 2022 Apr 6.