Abstract 1451
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.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract