Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial.

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 days 1-5 every 3 weeks) or weekly paclitaxel (80 mg/m) 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.

• Authors: Antonio González-Martín, Patricia Pautier, Sven Mahner, Joern Rau, Nicoletta Colombo, Petronella Ottevanger, Josep M Del Campo, Frédéric Selle, Andreas du Bois, Angiolo Gadducci, Yolanda García, Dominique Berton-Rigaud, Frederik Marmé, Eugenia Ortega, Nicolas Martin, Lydie Bastiere-Truchot, Astrid Kiermaier, Christian Kurzeder
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 26 Issue 5 Pg. 898-905 (06 2016) ISSN: 1525-1438 [Electronic] England
• PMID: 27206218 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Deoxycytidine
• Topotecan
• pertuzumab
• Paclitaxel
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cohort Studies
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Drug Resistance, Neoplasm
• Female
• Humans
• Middle Aged
• Organoplatinum Compounds (pharmacology)
• Ovarian Neoplasms (drug therapy)
• Paclitaxel (administration & dosage, adverse effects)
• Topotecan (administration & dosage, adverse effects)
• Gemcitabine