2015 American Society of Clinical Oncology Annual Meeting:
Significant Findings of a Sensitivity Analysis of Chemotherapy with or Without Pertuzumab in Platinum-Resistant Ovarian Cancer
Christian Kurzeder, MD, of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group and Kliniken Essen-Mitte, Essen, Germany, reported on the efficacy and safety of chemotherapy with or without pertuzumab for platinum-resistant ovarian cancer in the AGO-OVAR 2.20/ENGOT-ov14/PENELOPE double-blinded, placebo-controlled, randomized, phase 3 trial. Dr. Kurzeder presented his research at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO).
Chemotherapy + Pertuzumab Improved Progression-Free Survival in an Earlier Trial
In a 2010 trial led by Makhija,1 adding pertuzumab to gemcitabine for platinum-resistant ovarian cancer improved progression-free survival in a subset of patients with low-tumor HER3 mRNA expression.
AGO-OVAR 2.20/ENGOT-ov14/PENELOPE Trial
Eligible patients had recurrent platinum-resistant ovarian cancer progression during/within 6 months of completing ≥4 platinum cycles with centrally tested low tumor HER3 mRNA expression (concentration ratio ≤2.81 by quantitative reverse transcriptase polymerase chain reaction on the cobas® z480 [Roche Molecular Systems Inc., Pleasanton, CA) and ≤2 prior chemotherapy lines.
Investigators chose topotecan, paclitaxel, or gemcitabine chemotherapy. Recruitment was capped to ensure similarly sized chemotherapy cohorts.
Patients were stratified by chosen chemotherapy, prior antiangiogenic therapy, and platinum-free interval (<3 vs 3–6 months) and randomized 1:1 to chemotherapy with either placebo or pertuzumab 840→420 mg every 3 weeks until disease progression/unacceptable toxicity.
The primary objective was to determine whether progression-free survival was superior with pertuzumab + chemotherapy vs placebo + chemotherapy.
The prespecified primary progression-free survival analysis after 109 blinded progression-free survival events in 154 planned patients provided 95% power to detect a progression-free survival hazard ratio of 0.50 (median 1.4→2.8 months) with two-sided log-rank α = 0.05. Other measured endpoints included overall survival, progression-free survival, objective response rate, safety, and translational research.
Primary Endpoint Did Not Achieve Statistical Significance
From 2013 to 2014, 156 patients were randomized. Adding pertuzumab to chemotherapy improved progression-free survival (median 4.3 vs 2.6 months for placebo + chemotherapy). Significance was not achieved, however, for the primary endpoint analysis. Subgroup analyses by chemotherapy showed inconsistent results. No new safety signals were seen.
Though the primary objective of progression-free survival was not met, subgroup analyses showed trends favoring pertuzumab in the gemcitabine and paclitaxel cohorts, potentially explaining the significant findings in one of the sensitivity analyses. The results merit further exploration of pertuzumab in ovarian cancer.
June 30, 2015