PT - JOURNAL ARTICLE AU - González-Martín, Antonio AU - Pautier, Patricia AU - Mahner, Sven AU - Rau, Joern AU - Colombo, Nicoletta AU - Ottevanger, Petronella AU - del Campo, Josep M. AU - Selle, Frédéric AU - du Bois, Andreas AU - Gadducci, Angiolo AU - García, Yolanda AU - Berton-Rigaud, Dominique AU - Marmé, Frederik AU - Ortega, Eugenia AU - Martin, Nicolas AU - Bastiere-Truchot, Lydie AU - Kiermaier, Astrid AU - Kurzeder, Christian TI - Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial AID - 10.1097/IGC.0000000000000695 DP - 2016 Jun 01 TA - International Journal of Gynecologic Cancer PG - 898--905 VI - 26 IP - 5 4099 - http://ijgc.bmj.com/content/26/5/898.short 4100 - http://ijgc.bmj.com/content/26/5/898.full SO - Int J Gynecol Cancer2016 Jun 01; 26 AB - Objective In platinum-resistant ovarian cancer, adding pertuzumab to gemcitabine improved progression-free survival in the subgroup with low tumor HER3 messenger RNA expression. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population.Patients and Methods Part 1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients with platinum-refractory or platinum-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer and low HER3 messenger RNA expression (concentration ratio ≤2.81 by central quantitative reverse transcriptase-polymerase chain reaction testing on Cobas z480) received intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) with the investigator’s choice of topotecan (1.25 mg/m2 days 1–5 every 3 weeks) or weekly paclitaxel (80 mg/m2) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability.Results Fifty patients were treated in part 1 (22 topotecan; 28 paclitaxel). In both cohorts, disease progression was the most common primary reason for discontinuing pertuzumab, and the most common all-grade adverse events (AEs) were fatigue/asthenia, anemia, and diarrhea. The most common grade ≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%) for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%) for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from AEs (abdominal infection; unexplained death). Median progression-free survival was 4.1 months (95% confidence interval, 1.9–6.1) with topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5–6.0) with paclitaxel-pertuzumab.Conclusions Based on part 1 tolerability, the Independent Data Monitoring Committee had no objection to PENELOPE proceeding to part 2, a double-blind randomized comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus pertuzumab or placebo.