Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study

Background: Most patients with ovarian cancer will relapse after receiving frontline platinum-based chemotherapy and eventually develop platinum-resistant or platinumrefractory disease.We report results of avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) compared with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200 trial). Methods:In this open-label, phase 3 trial, eligible women aged ≥18 years with epithelial ovarian, fallopian tube, or peritoneal cancer (maximum of 3 prior lines for platinum-sensitive disease, none for platinum-resistant disease) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomised (1:1:1) via interactive response technology to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m 2 intravenously every 4 weeks), or PLD and stratified by disease platinum status (refractory vs resistant), number of prior anticancer regimens (1 vs 2 or 3), and bulky disease (tumour size ≥5 vs <5 cm).Primary endpoints were progression-free survival by blinded independent central review and overall survival in all randomised patients, with the objective to demonstrate that avelumab alone or avelumab plus PLD would be superior to PLD.This trial is registered with ClinicalTrials.gov,number NCT02580058.The trial is no longer enrolling patients and this is the final analysis of both primary endpoints.Findings: Between January 5, 2016 and May 16, 2017, 566 patients were randomised.At data cutoff (September 19, 2018), median duration of follow-up for overall survival was 18•4 months (interquartile range [IQR] 15•6-21•9) for the combination arm, 17•4 months (IQR 15•2-21•3) for the PLD arm, and 18•2 months (IQR 15•8-21•2) for the avelumab arm.Improvement in progression-free survival by blinded independent central review or overall survival with avelumab plus PLD vs PLD alone did not reach statistical significance (hazard ratios, 0•78 [repeated CI 0•59-1•24; one-sided P=0•030] and 0•89 [repeated CI 0•74-1•24; one-sided P=0•21]).Avelumab alone did not improve progression-free survival by blinded