1451 - Randomized phase 3 trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese subgroup analysis

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.