TY - JOUR
T1 - Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer
T2 - Safety Run-in Results of the PENELOPE Trial
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
N1 - Publisher Copyright:
Copyright © 2016 by IGCS and ESGO.
PY - 2016/6/1
Y1 - 2016/6/1
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.
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.
KW - HER3
KW - Ovarian cancer
KW - Pertuzumab
KW - Phase 3
KW - Platinum-resistant
UR - http://www.scopus.com/inward/record.url?scp=84973322877&partnerID=8YFLogxK
U2 - 10.1097/IGC.0000000000000695
DO - 10.1097/IGC.0000000000000695
M3 - Article
C2 - 27206218
AN - SCOPUS:84973322877
SN - 1048-891X
VL - 26
SP - 898
EP - 905
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 5
ER -