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.