Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial. Issue 5 (1st June 2016)

• Record Type: Journal Article
• Authors: González-Martín, Antonio; Pautier, Patricia; Mahner, Sven; Rau, Joern; Colombo, Nicoletta; Ottevanger, Petronella; del Campo, Josep M.; Selle, Frédéric; du Bois, Andreas; Gadducci, Angiolo; García, Yolanda; Berton-Rigaud, Dominique; Marmé, Frederik; Ortega, Eugenia; Martin, Nicolas; Bastiere-Truchot, Lydie; Kiermaier, Astrid; Kurzeder, Christian
• Is Part Of: International journal of gynecological cancer. Volume 26:Issue 5(2016)
• Page Start: 898
• Page End: 905
• Publication Date: 2016-06-01
• Subjects: HER3 -- Ovarian cancer -- Pertuzumab -- Platinum-resistant -- Phase 3; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1097/IGC.0000000000000695
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : 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/m 2 days 1–5 every 3 weeks) or weekly paclitaxel (80 mg/m 2 ) 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.