TY - JOUR T1 - Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 898 LP - 905 DO - 10.1097/IGC.0000000000000695 VL - 26 IS - 5 AU - Antonio González-Martín AU - Patricia Pautier AU - Sven Mahner AU - Joern Rau AU - Nicoletta Colombo AU - Petronella Ottevanger AU - Josep M. del Campo AU - Frédéric Selle AU - Andreas du Bois AU - Angiolo Gadducci AU - Yolanda García AU - Dominique Berton-Rigaud AU - Frederik Marmé AU - Eugenia Ortega AU - Nicolas Martin AU - Lydie Bastiere-Truchot AU - Astrid Kiermaier AU - Christian Kurzeder Y1 - 2016/06/01 UR - http://ijgc.bmj.com/content/26/5/898.abstract N2 - 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. ER -