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. 2023 Dec;8(6):102034.
doi: 10.1016/j.esmoop.2023.102034. Epub 2023 Oct 20.

Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101

Y Tomita  1 , R J Motzer  2 , T K Choueiri  3 , B I Rini  4 , H Miyake  5 , M Oya  6 , L Albiges  7 , M Aizawa  8 , Y Umeyama  8 , J Wang  9 , A di Pietro  10 , M Schmidinger  11
Affiliations

Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101

Y Tomita et al. ESMO Open. 2023 Dec.

Abstract

Background: In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline.

Methods: Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.1) and OS. Best percentage change and percentage change from baseline in target tumor size over time during the study were also assessed.

Results: In patients with 0, 1, 2, 3, or 4-6 IMDC risk factors, hazard ratios [HRs; 95% confidence interval (CIs)] for OS with avelumab + axitinib versus sunitinib were 0.660 (0.356-1.223), 0.745 (0.524-1.059), 0.973 (0.668-1.417), 0.718 (0.414-1.248), and 0.443 (0.237-0.829), and HRs (95% CIs) for PFS were 0.706 (0.490-1.016), 0.709 (0.540-0.933), 0.711 (0.527-0.960), 0.501 (0.293-0.854), and 0.395 (0.214-0.727), respectively. In patients with 1, 2, 3, or ≥4 target tumor sites, HRs (95% CIs) for OS with avelumab + axitinib versus sunitinib were 0.912 (0.640-1.299), 0.715 (0.507-1.006), 0.679 (0.442-1.044), and 0.747 (0.346-1.615), and HRs (95% CIs) for PFS were 0.706 (0.548-0.911), 0.552 (0.422-0.723), 0.856 (0.589-1.244), and 0.662 (0.329-1.332), respectively. Across all subgroups, analyses of objective response rate and complete response rate favored avelumab + axitinib versus sunitinib, and a greater proportion of patients treated with avelumab + axitinib had tumor shrinkage.

Conclusions: In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.

Keywords: avelumab; axitinib; renal cell carcinoma; risk factor; tumor site.

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Conflict of interest statement

Disclosure YT has participated in consulting or advisory roles for Eisai, Merck Sharp & Dohme (MSD), and Ono Pharmaceutical; has received honoraria from Astellas Pharma, Bristol Myers Squibb Japan, Chugai Pharma, Novartis, Ono Pharmaceutical, and Pfizer; and has received research funding from Astellas Pharma, AstraZeneca, Chugai Pharma, Eisai, MSD, Novartis, Ono Pharmaceutical, Pfizer, and Takeda. RJM has participated in consulting or advisory roles for AstraZeneca, Aveo, Calithera Biosciences, Eisai, Exelixis, Genentech/Roche, Incyte, Pfizer, and EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; 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 EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. TKC reports institutional and personal, paid and/or unpaid support for research, advisory boards, consultancy, and honoraria from Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, CME events (Peerview, OncLive, MJH and others), Eisai, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Exelixis, GlaxoSmithKline, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, MSD, NiKang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, and Up-To-Date, outside the submitted work; reports institutional patents filed on molecular alterations and immunotherapy response/toxicity, and circulating tumor DNA; reports equity Osel, Pionyr, Precede Bio, and Tempest; has served in committees for ACCRU, ASCO/ESMO, GU Steering Committee, KidneyCan, and NCCN; reports that medical writing and editorial assistance support may have been funded by communications companies in part; 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 or/and 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. BIR has participated in consulting or advisory roles for 3D Medicines, Aravive, Arrowhead Pharmaceuticals, Aveo, Bristol Myers Squibb, Corvus Pharmaceuticals, Eisai, GlaxoSmithKline, Pfizer, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Shionogi, Surface Oncology, and Synthorx; reports leadership with MJH Life Sciences; has received travel, accommodations, and expenses from Bristol Myers Squibb, Pfizer, and EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; 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, Seagen, Surface Oncology, Taris, and EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. HM has received honoraria, consulting or advisory fees, and research funding from Pfizer. MO has participated in consulting or advisory roles for Bayer; has received honoraria from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb Japan, Chugai Pharma, Janssen, MSD, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, and Takeda; and has received research funding from Astellas Pharma. LA has participated in consulting or advisory roles for Astellas Pharma, AstraZeneca, Bellerophon Therapeutics, Bristol Myers Squibb, Corvus Pharmaceuticals, Eisai, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer, and Roche; has received travel, accommodations, and expenses from Bristol Myers Squibb and MSD; and has received research funding from Bristol Myers Squibb. MA is an employee of Pfizer R&D Japan. YU is an employee of Pfizer R&D Japan and holds stock in Pfizer. JW is an employee and reports stock and other ownership interest with Pfizer. AdiP reports employment, stock, and other ownership interest with Pfizer, and has received honoraria from Pfizer. MS has participated in 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.

Figures

Figure 1
Figure 1
OS in the overall population (A), by number of IMDC risk factors (B-F), and by number of target tumor sites (G-J). (A) Overall population. (B) 0 IMDC risk factors (favorable risk). (C) 1 IMDC risk factor (intermediate risk). (D) 2 IMDC risk factors (intermediate risk). (E) 3 IMDC risk factors (poor risk). (F) 4-6 IMDC risk factors (poor risk). (G) 1 Target tumor site. (H) 2 Target tumor sites. (I) 3 Target tumor sites. (J) ≥4 Target tumor sites. Figure 1A and B was reprinted from Haanen JBAG et al. Copyright © 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. CI, confidence interval; HR, hazard ratio; IMDC, International Metastatic RCC Database Consortium; NE, not estimable; NR, not reached; OS, overall survival; RCC, renal cell carcinoma.
Figure 2
Figure 2
PFS per investigator assessment in the overall population (A), by number of IMDC risk factors (B-F), and by number of target tumor sites (G-J). (A) Overall population. (B) 0 risk IMDC factors (favorable risk). (C) 1 IMDC risk factor (intermediate risk). (D) 2 IMDC risk factors (intermediate risk). (E) 3 IMDC risk factors (poor risk). (F) 4-6 IMDC risk factors (poor risk). (G) 1 Target tumor site. (H) 2 Target tumor sites. (I) 3 Target tumor sites. (J) ≥4 Target tumor sites. Figure 2A and B was reprinted from Haanen JBAG et al. Copyright © 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. CI, confidence interval, HR, hazard ratio; IMDC, International Metastatic RCC Database Consortium; PFS, progression-free survival; RCC, renal cell carcinoma.
Figure 3
Figure 3
ORR and CR rate per investigator assessment in the overall population and subgroups defined by (A) number of IMDC risk factors and (B) number of target tumor sites. The odds ratio is stratified for the overall population and unstratified for subgroups. CI, confidence interval; CR, complete response; IMDC, International Metastatic RCC Database Consortium; ORR, objective response rate; PR, partial response; RCC, renal cell carcinoma.
Figure 4
Figure 4
Percentage change from baseline in target tumor size over time per investigator assessment by number of IMDC risk factors. (A) 0 IMDC risk factors (favorable risk). (B) 1 IMDC risk factor (intermediate risk). (C) 2 IMDC risk factors (intermediate risk). (D) 3 IMDC risk factors (poor risk). (E) 4-6 IMDC risk factors (poor risk). IMDC, International Metastatic RCC Database Consortium; LOESS, locally estimated scatterplot smoothing; RCC, renal cell carcinoma.
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