Randomized phase III trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN renal 101 Japanese subgroup analysis

Abstract

Background: Avelumab is a human IgG1 monoclonal antibody against PD‐L1, and axitinib is a potent inhibitor of VEGFR 1, 2, and 3. In a phase 3 study in patients (pts) with treatment‐naive advanced renal cell carcinoma (aRCC; NCT02684006), avelumab in combination with axitinib (A+Ax) significantly improved progression‐free survival (PFS) irrespective of PD‐L1 expression vs sunitinib (S) at the preplanned interim analysis; median PFS was 13.8 mo with A+Ax vs 8.4 mo with S (HR, 0.69; p = 0.0001). Here, we report efficacy and safety in Japanese pts who were enrolled in this study. Methods: Eligible pts with clear‐cell aRCC, ECOG PS ≤ 1, and no prior systemic therapy were randomized 1:1 (stratified by ECOG PS and geographic region) to receive A 10 mg/kg IV Q2W + Ax 5 mg PO BID or S 50 mg PO QD on schedule 4/2. Primary endpoints were PFS by blinded independent central review (BICR) per RECIST v1.1 and overall survival (OS) in pts with PD‐L1+ tumors (≥1% of immune cells). Key secondary endpoints were PFS by BICR and OS irrespective of PD‐L1 expression. Other secondary endpoints included objective response rate (ORR), and safety. Results: Japanese pts (N = 67) were randomized to A+Ax (n = 33) or S (n = 34); 67% vs 59% had PD‐L1+ tumors; IMDC favorable/intermediate/poor risk status was 6%/64%/27% vs 6%/82%/12%. Median PFS (95% CI) was not estimable (NE) (8.1‐NE) with A+Ax vs 11.2 months (1.6‐NE) with S (HR, 0.49; 95%CI, 0.15‐1.56) in pts with PD‐L1+ tumors and 16.6 mo (8.1‐NE) with A+Ax vs 11.2 mo (4.2‐NE) with S (HR, 0.66; 95% CI, 0.30‐1.46) in pts irrespective of PD‐L1 expression. Median OS in either arm has not been reached in pts irrespective of PD‐L1 expression. ORR (95% CI) was 60.6% (42.1%‐77.1%) with A+Ax vs 17.6% (6.8%‐34.5%) with S in pts 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%). Conclusions: A+Ax was efficacious and tolerable in Japanese pts with treatment‐naive aRCC, which is consistent with results in the overall population. Clinical trial identification: NCT02684006, Feb 17, 2016. Editorial acknowledgement: Clinical Thinking, a Nucleus Global Company, Hamilton, NJ, USA. Legal entity responsible for the study: Pfizer, Inc. Funding: Funding for this study was provided by Pfizer, Inc. in alliance with Merck Healthcare KGaA, Darmstadt, Germany. Disclosure: Y. Tomita: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (self): Sanofi‐Aventis; Honoraria (self): BMS; Advisory / Consultancy: Taiho; Advisory / Consultancy: MSD; Research grant / Funding (institution): Takeda. S. Hatakeyama: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): Kissei; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Research grant / Funding (institution): Ono; Research grant / Funding (institution): Bristol; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Kaneka. H. Kanayama: Honoraria (self), Research grant / Funding (institution): Pfizer. K. Numakura: Honoraria (self): Pfizer; Honoraria (self): Astellas; Honoraria (self): Ono Pharm; Honoraria (self): Kyowa Kirin; Honoraria (self): AstraZeneca; Research grant / Funding (self): Grants‐in‐Aid for Scientific Research, the ministry of Education, Japan. T. Kato: Honoraria (self): Pfizer, Inc.; Honoraria (self): Novartis Pharma K.K; Honoraria (self): ONO Pharmaceutical Co., Ltd.; Honoraria (self): TAIHO Pharmaceutical Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Bayer Yakuhin, Ltd.; Honoraria (self): Astellas Pharma Inc. M. Eto: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ono; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Bayer. H. Uemura: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ono; Honoraria (self), Speaker Bureau / Expert testimony: BMS; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony: Bayer; Research grant / Funding (self): Taiho; Research grant / Funding (self): Astellas; Research grant / Funding (self): Ono. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer, Inc.; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Bristol‐Myers Squibb (BMS); Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy: Merck. Y. Fujii: Full / Part‐time employment: Pfizer R&D Japan. Y. Kamei: Full / Part‐time employment: Pfizer R&D Japan. M. Oya: Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Ono; Honoraria (self): BMS. All other authors have declared no conflicts of interest.