Abstract 292P
Background
In the phase III JAVELIN Renal 101 trial (NCT02684006), first-line A + Ax showed significantly longer progression-free survival (PFS), a higher objective response rate (ORR), and an acceptable safety profile vs S in pts with aRCC, including in subgroups defined by age. At the final analysis (follow-up, ≥68 months), overall survival (OS) favored A + Ax vs S, but results did not reach statistical significance. We report updated efficacy and safety results in subgroups defined by age using data from the final analysis.
Methods
Pts were randomized 1:1 to receive A + Ax or S. PFS and ORR per investigator assessment (RECIST 1.1), OS, and safety were assessed in pts aged <65, 65 to <75, or ≥75 y. OS and PFS were analyzed using the Kaplan-Meier method.
Results
At data cutoff (31 Aug 2023), median follow-up for OS in the A + Ax and S arms was 73.7 and 73.6 months, respectively. In the A + Ax and S arms, 271/138/33 and 275/128/41 pts were aged <65, 65 to <75, or ≥75 y respectively. Baseline characteristics were generally well balanced across age subgroups in each arm; the highest proportion of pts with 1 International metastatic RCC Database Consortium risk factor (vs 0, 2, 3, or ≥4) was observed in pts aged ≥75 y in the A + Ax arm. OS, PFS, and ORR by age subgroups are shown in the table. In pts aged <65, 65 to <75, or ≥75 y, any-grade treated-related adverse events (TRAEs) occurred in 95.9%/97.7%/100.0% in the A + Ax arm and 95.2%/99.2%/100.0% in the S arm, respectively, with grade ≥3 TRAEs in 62.7%/75.9%/63.6% and 55.3%/73.0%/67.5%, respectively. Immune-related adverse events occurred in 50.7%/51.9%/39.4% in the A + Ax arm, respectively. Table: 292P
| <65 years | 65 to <75 years | ≥75 years | ||||
| A + Ax n=271 | S n=275 | A + Ax n=138 | S n=128 | A + Ax n=33 | S n=41 | |
| mOS, (95% CI), months | 46.9 (39.8-55.5) | 38.0 (27.6-49.3) | 43.8 (31.2-52.0) | 44.7 (32.6-59.2) | 33.1 (23.0-63.3) | 29.4 (18.6-37.8) |
| Unstratified HR (95% CI) | 0.84 (0.68-1.03) | 1.01 (0.75-1.36) | 0.79 (0.45-1.37) | |||
| mPFS, (95% CI), months* | 12.9 (9.8-17.8) | 7.9 (6.6-8.5) | 14.1 (11.1-20.6) | 11.3 (9.7-14.0) | 14.1 (8.7-19.7) | 10.0 (7.0-18.6) |
| Unstratified HR (95% CI) | 0.62 (0.51-0.75) | 0.84 (0.63-1.1) | 0.67 (0.38-1.2) | |||
| ORR (95% CI), %* | 60.5 (54.4-66.4) | 31.3 (25.8-37.1) | 62.3 (53.7-70.4) | 33.6 (25.5-42.5) | 42.4 (25.5-60.8) | 31.7 (18.1-48.1) |
*Per investigator assessment. m, median.
Conclusions
Subgroup analyses from JAVELIN Renal 101 confirmed the long-term efficacy and manageable safety profile of A+ Ax across age subgroups, including pts aged ≥75 y. Hazard ratios for OS and PFS were lower in pts aged <65 or ≥75 y vs pts aged 65 to <75 y.
Clinical trial identification
NCT02684006, first posted, February 17, 2016.
Editorial acknowledgement
Medical writing support was provided by Katherine Quiroz-Figueroa of Nucleus Global.
Legal entity responsible for the study
Pfizer, as part of a previous alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer.
Funding
This trial was sponsored by Pfizer and was previously conducted under an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer. This analysis was sponsored by Merck.
Disclosure
M. Oya: Financial Interests, Personal, Other, honoraria: Bayer, Bristol Myers Squibb, Eisai, Merck Biopharma Co., Ltd., Tokyo, Japan, an affiliate of Merck KGaA, MSD, Ono, Pfizer, Takeda; Financial Interests, Personal, Other, manuscript fees: Pfizer; Financial Interests, Personal, Other, scholarship endowments: Bayer, Eisai, Ono, Takeda. R.J. Motzer: Financial Interests, Personal, Advisory Role: AstraZeneca, Aveo, Calithera Biosciences, Eisai, Exelixis, Genentech/Roche, Incyte, Merck, Pfizer; Financial Interests, Personal, Other, travel, accommodations, and expenses: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Aveo, Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, Novartis, Merck , Pfizer. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; 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