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. 2023 Jun;8(3):101210.
doi: 10.1016/j.esmoop.2023.101210. Epub 2023 Apr 25.

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma

J B A G Haanen  1 , J Larkin  2 , T K Choueiri  3 , L Albiges  4 , B I Rini  5 , M B Atkins  6 , M Schmidinger  7 , K Penkov  8 , E Michelon  9 , J Wang  10 , M Mariani  11 , A di Pietro  11 , R J Motzer  12
Affiliations

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma

J B A G Haanen et al. ESMO Open. 2023 Jun.

Abstract

Background: We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial.

Patients and methods: Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed.

Results: Overall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization.

Conclusions: Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing.

Trial registration: ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

Keywords: avelumab; immunotherapy; phase III; renal cell carcinoma; risk factor.

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Conflict of interest statement

JBAGH has provided consulting or advisory roles for Achilles Therapeutics, AIMM Therapeutics, Bristol Myers Squibb, Immunocore, Ipsen, MSD, Neogene Therapeutics, Neon Therapeutics, Novartis, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, and Third Rock Ventures; and has received research funding from Amgen, Bristol Myers Squibb, MSD, Neon Therapeutics, and Novartis. JL has received honoraria from Bristol Myers Squibb, CRUK, Dynavax, Eisai, GSK, Incyte, iOnctura, Merck, Novartis, Pfizer, Roche, touchEXPERTS, and touchIME; has provided consulting or advisory roles for Apple Tree, Boston Biomedical, Bristol Myers Squibb, GSK, Immunocore, Incyte, iOnctura, Iovance, Novartis, Pfizer, and YKT Global; has received speaker fees from Aptitude, AstraZeneca, Bristol Myers Squibb, Calithera, Eisai, Ervaxx, EUSA Pharma, GSK, Incyte, Ipsen, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, and Ultimovacs; has received institutional research funding from Achilles Therapeutics, Aveo, Bristol Myers Squibb, Covance, Immunocore, MSD, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, and Roche; and has received grants from Achilles Therapeutics, Aveo, Bristol Myers Squibb, Immunocore, MSD, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, and Roche. TKC reports institutional and personal, paid and unpaid support for research, advisory boards, consultancy, and honoraria from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, Merck, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, UpToDate, and CME events (PeerView, OncLive, MJH, and others), outside the submitted work; reports institutional patents filed on molecular alterations and immunotherapy response/toxicity and ctDNA; reports equity for Osel, Pionyr, Precede Bio, and Tempest; has served in committees for NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, and KidneyCAN; reports that medical writing and editorial assistance support may have been funded by communications companies in part; reports no speaker’s bureau; has mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/foreign components; reports that the institution (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies and/or royalties potentially involved in research around the subject matter; and is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, and Loker Pinard Funds for Kidney Cancer Research at DFCI. LA has provided consulting or advisory roles for Astellas Pharma, Bristol Myers Squibb, Eisai, Janssen, Ipsen, MSD, Novartis, Pfizer, and Roche; and has received travel, accommodations, and expenses from Bristol Myers Squibb, Ipsen, and MSD. BIR has provided consulting or advisory roles for 3D Medicines, Aravive, Arrowhead Pharmaceuticals, Aveo, Bristol Myers Squibb, Corvus Pharmaceuticals, Eisai, GlaxoSmithKline, Pfizer, Merck, Shionogi, Surface Oncology, and Synthorx; reports leadership with MJH Life Sciences; has received travel, accommodations, and expenses from Bristol Myers Squibb, Pfizer, and Merck; reports stock and other ownership interests from PTC Therapeutics; and has received research funding from Aravive, Arrowhead Pharmaceuticals, AstraZeneca/MedImmune, Bristol Myers Squibb, Dragonfly Therapeutics, Immunomedics, Incyte, Exelixis, Pfizer, Roche/Genentech, Seattle Genetics, Surface Oncology, Taris, and Merck. MBA has provided consulting or advisory roles for Genentech/Roche, Novartis, Bristol Myers Squibb, MSD, Exelixis, Eisai, Agenus, Arrowhead Pharmaceuticals, Werewolf Pharma, Surface Oncology, Iovance Biotherapeutics, Pyxis, Pneuma Respiratory, Leads Biolabs, Fathom Biotechnology, Aveo, Cota Healthcare, Neoleukin Therapeutics, Adagene, Idera, Ellipses Pharma, AstraZeneca, PACT Pharma, Asher Biotherapeutics, Seagen, Pfizer, Scholar Rock, Simcha Therapeutics, Takeda, Calithera Biosciences, and Sanofi; reports stock and other ownership interests in Werewolf Pharma and Pyxis; and has received institutional research funding from Bristol Myers Squibb. MS has provided consulting or advisory roles for Bristol Myers Squibb, Eisai, EUSA Pharma, Ipsen, MSD, and Roche; has received travel, accommodations, and expenses from Bristol Myers Squibb, Ipsen, and Roche; and has received honoraria from Alkermes, Bristol Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen Oncology, and MSD. KP has received honoraria from Roche, Pfizer, Nektar, MSD, Regeneron, and AstraZeneca; and has provided consulting or advisory roles for Nektar. EM reports employment, stock, and other ownership interest with Pfizer. JW reports employment, stock, and other ownership interest with Pfizer. MM reports employment, stock, and other ownership interest with Pfizer. AdP reports employment, stock, and other ownership interest with Pfizer; and has received honoraria from Pfizer. RJM has provided consulting or advisory roles for AstraZeneca, Aveo, Calithera Biosciences, Eisai, Exelixis, Genentech/Roche, Incyte, Pfizer, and Merck; has received travel, accommodations, and expenses from Bristol Myers Squibb; and has received research funding from Aveo, Bristol Myers Squibb, Eisai, Exelixis, Genentech/Roche, Novartis, Pfizer, and Merck.

Figures

Figure 1
Figure 1
Kaplan–Meier analysis of (A) overall survival (OS) and (B) progression-free survival (PFS) in the overall population. HR, hazard ratio; NE, not estimable.
Figure 2
Figure 2
Kaplan–Meier analysis of overall survival (OS) and progression-free survival (PFS) by IMDC subgroups. (A) OS in the favorable-risk subgroup. (B) PFS in the favorable-risk subgroup. (C) OS in the intermediate-risk subgroup. (D) PFS in the intermediate-risk subgroup. (E) OS in the poor-risk subgroup. (F) PFS in the poor-risk subgroup. CI, confidence interval; HR, hazard ratio; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; NE, not estimable.
See this image and copyright information in PMC

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