Background: Adding P to gemcitabine (GEM) for PROC improved progression-free survival (PFS) in a subset of patients (pts) with low tumor HER3 mRNA expression [Makhija 2010]. Methods: Eligible pts had recurrent PROC (progression [PD] during/within 6 mo of completing ≥ 4 platinum cycles) with centrally tested low tumor HER3 mRNA expression (concentration ratio ≤ 2.81 by qRT-PCR on cobas z480) and ≤ 2 prior CT lines. Investigators (INVs) chose CT (topotecan [TOP], paclitaxel [PAC] or GEM); recruitment was capped to ensure similarly sized CT cohorts. Pts were stratified by chosen CT, prior anti-angiogenic therapy and platinum-free interval ( < 3 vs 3–6 mo) and randomized 1:1 to CT with either placebo or P 840→420 mg q3w until PD/unacceptable toxicity. The primary objective was to determine if independent review committee (IRC)-assessed PFS was superior with P + CT vs placebo + CT. The prespecified primary PFS analysis after 109 blinded IRC-assessed PFS events in 154 planned pts provided 95% power to detect a PFS hazard ratio (HR) of 0.50 (median 1.4→2.8 mo) with 2-sided log-rank α = 0.05. Other endpoints include overall survival, INV-assessed PFS, objective response rate, safety and translational research. Results: From Oct 2013 to Sep 2014, 156 pts were randomized. Adding P to CT improved PFS (median 4.3 mo vs 2.6 mo for placebo + CT); however, significance was not achieved for the primary endpoint analysis. Subgroup analyses by CT showed inconsistent results. No new safety signals were seen. Conclusion: Although the primary objective was not met, subgroup analyses showed trends favoring P in the GEM and PAC cohorts, potentially explaining the significant findings in one of the sensitivity analyses. These results merit further exploration of P in ovarian cancer. Clinical trial information: NCT01684878

*Recruitment to TOP was slowest.