Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Mar;111(3):907-923.
doi: 10.1111/cas.14294. Epub 2020 Feb 5.

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Motohide Uemura  1 , Yoshihiko Tomita  2 , Hideaki Miyake  3 , Shingo Hatakeyama  4 , Hiro-Omi Kanayama  5 , Kazuyuki Numakura  6 , Toshio Takagi  7 , Tomoyuki Kato  8 , Masatoshi Eto  9 , Wataru Obara  10 , Hirotsugu Uemura  11 , Toni K Choueiri  12 , Robert J Motzer  13 , Yosuke Fujii  14 , Yoichi Kamei  14 , Yoshiko Umeyama  14 , Alessandra di Pietro  15 , Mototsugu Oya  16
Affiliations
Clinical Trial

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

Motohide Uemura et al. Cancer Sci. 2020 Mar.

Abstract

The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment-naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression-free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD-L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD-L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD-L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD-L1+ tumors and irrespective of PD-L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD-L1 expression. Common treatment-emergent adverse events (all grade; grade ≥3) in each arm were hand-foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment-naive Japanese patients with advanced RCC, which is consistent with results in the overall population.

Keywords: Japan; avelumab; axitinib; phase 3 JAVELIN Renal 101 clinical trial; renal cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

Motohide Uemura has nothing to disclose. Yoshihiko Tomita has received honoraria from Pfizer, Astellas, Novartis, Ono, Sanofi‐Aventis and BMS; reports a consulting or advisory role for Novartis, Ono, Taiho and MSD; and reports institutional research funding from Pfizer, Ono, Takeda and Astellas. Hideaki Miyake has nothing to disclose. Shingo Hatakeyama has received honoraria from Pfizer, Astellas, Kissei, Sanofi and Ono; and reports institutional research funding from Pfizer, Astellas, Kissei, Sanofi, Ono, Bristol, Janssen and Kaneka. Hiro‐omi Kanayama has received honoraria from Pfizer and reports institutional research funding from Pfizer. Kazuyuki Numakura has received honoraria from Pfizer, Astellas, Ono, Kyowa Kirin and AstraZeneca, and research funding from the Ministry of Education (Japan; Grants‐in‐Aid for Scientific Research). Toshio Takagi has received honoraria from Novartis, Ono and BMS. Tomoyuki Kato has received honoraria from Pfizer, Novartis, Ono, Taiho, Chugai, Bayer and Astellas. Masatoshi Eto has received honoraria from Ono, BMS, Pfizer, Novartis and Bayer; reports a consulting or advisory role for Ono, BMS, Pfizer and Novartis; and has received research funding from Ono, Pfizer, Novartis and Bayer. Wataru Obara has nothing to disclose. Hirotsugu Uemura has received honoraria from Ono, BMS, AstraZeneca, MSD and Janssen; reports a consulting or advisory role for Sanofi and Ono; is a member of a speaker’s bureau for MSD, Janssen, BMS, Pfizer and Bayer; and has received research funding from Pfizer, Janssen, Taiho, AstraZeneca, Astellas, Takeda and Ono. Toni K. Choueiri reports grants received during the conduct of the study from Pfizer; personal fees received outside the conduct of the study from Agensys, Alexion, Alligent, American Society of Clinical Oncology, Analysis Group, AstraZeneca, Bayer, Bristol‐Myers Squibb, Celldex, Cerulean, Clinical Care Options, Corvus, Dana‐Farber Cancer Institute, EMD Serono, Eisai, Exelixis, Foundation Medicine, Genentech/Roche, GSK, Harborside Press, Heron, Ipsen, Kidney Cancer Association, Kidney Cancer Journal, L‐path, Lancet Oncology, Lilly, Merck, Michael J. Hennessy Associates, National Comprehensive Cancer Network, Navinata Health, New England Journal of Medicine, Novartis, Peloton Therapeutics, Pfizer, PlatformQ Health, Prometheus Laboratories, Sanofi/Aventis, Seattle Genetics/Astellas and UpToDate; grants received outside the conduct of the study from AstraZeneca, Bayer, Bristol‐Myers Squibb, Calithera, Cerulean, Corvus, Eisai, Exelixis, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Ipsen, Merck, Novartis, Peloton Therapeutics, Pfizer, Prometheus Laboratories, Takeda and Tracon; and medical writing and editorial assistance provided by ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions and Parexel, and funded by pharmaceutical companies. Robert J. Motzer reports grants and personal fees from Pfizer, Novartis, Eisai and Genentech/Roche, personal fees from Exelixis, Merck and Incyte, and grants from BMS and GSK outside the submitted work. Yosuke Fujii is an employee of Pfizer R&D Japan. Yoichi Kamei is an employee of Pfizer R&D Japan. Yoshiko Umeyama is an employee of Pfizer R&D Japan and reports stock ownership in Pfizer. Alessandra di Pietro is an employee of Pfizer and reports stock ownership in Pfizer. Mototsugu Oya has received honoraria from Pfizer, Novartis, Bayer, Ono and BMS; reports a consulting or advisory role for Bayer; and has received research funding from Pfizer and Novartis.

Figures

Figure 1
Figure 1
PFS per BICR in patients with PD‐L1+ tumors in the overall population (A) and Japanese patients (B) and in patients irrespective of PD‐L1 expression in the overall population (C) and Japanese patients (D). BICR, blinded independent central review; CI, confidence interval; HR, hazard ratio; NE, not estimable; PD‐L1, programmed death‐ligand 1; PFS, progression‐free survival. Data for overall population are from reference 23. Copyright © 2019 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society
Figure 2
Figure 2
Duration of treatment and time to and duration of response with avelumab + axitinib per BICR in Japanese patients irrespective of PD‐L1 expression (N = 33). Vertical axis label: ECOG PS from IRT system; IMDC risk category; and best overall response based on BICR assessment. The thin bar indicates axitinib treatment once daily. Patient 21 temporarily stopped axitinib, but the permanent discontinuation of axitinib had not been judged by the investigator at the data cutoff date. It is recorded in the clinical database that the treatment with axitinib was still ongoing for this patient. BICR, blinded independent central review; CR, complete response; OR, objective response; PD, progressive disease; PD‐L1, programmed death‐ ligand 1; PR, partial response; PS, performance status; SD, stable disease
Figure 3
Figure 3
Best percentage change from baseline in target lesions per BICR in Japanese patients irrespective of PD‐L1 expression who received avelumab + axitinib (A) or sunitinib (B). BICR, blinded independent central review; BOR, best overall response; CR, complete response; NE, not evaluable; PD, progressive disease; PD‐L1, programmed death‐ligand 1; PR, partial response; SD, stable disease
Figure 4
Figure 4
Percent change from baseline in target lesions per BICR in Japanese patients irrespective of PD‐L1 expression who received avelumab + axitinib (A) or sunitinib (B). BICR, blinded independent central review; BOR, best overall response; CR, complete response; NE, not evaluable; PD, progressive disease; PD‐L1, programmed death‐ligand 1; PR, partial response; SD, stable disease
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Choueiri TK, Motzer RJ. Systemic therapy for metastatic renal‐cell carcinoma. N Engl J Med. 2017;376:354‐366. - PubMed
    1. Kidney cancer early detection, diagnosis, and staging. https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging..... Accessed May 10, 2019.
    1. National Comprehensive Cancer Network . NCCN guidelines: Kidney cancer. 2019. https://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf. Accessed May 10, 2019.
    1. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal‐cell carcinoma. N Engl J Med. 2007;356:115‐124. - PubMed
    1. Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy‐refractory metastatic Merkel cell carcinoma: a multicentre, single‐group, open‐label, phase 2 trial. Lancet Oncol. 2016;17:1374‐1385. - PMC - PubMed

Publication types

MeSH terms