Lurbinectedin (PM01183), an active compound in platinum-resistant/refractory ovarian cancer (PRROC) patients: Results of a two-stage, controlled phase II study.

Gynecologic Cancer
Session Type and Session Title: 
Oral Abstract Session, Gynecologic Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5505)
Andres Poveda, Dominique Berton-Rigaud, Isabelle Laure Ray-Coquard, Jérôme Alexandre, Magali Provansal, Arturo Soto, Carmen Maria Kahatt, Sergio A. Szyldergemajn, Antonio Nieto, Cristian Fernandez, Eva Guerra Alia, Antonio Casado, Antonio Gonzalez-Martin, Jose Maria Del Campo; Instituto Valenciano de Oncologia, Valencia, Spain; ICO Centre René Gauducheau, Saint-Herblain, France; Centre Léon Bérard, Lyon, France; Cochin Hospital, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Institut Paoli Calmettes, Marseille, France; PharmaMar, Madrid, Spain; Hospital Universitario Ramón y Cajal, Madrid, Spain; Hospital Clinico San Carlos, Madrid, Spain; Medical Oncology Service, Centro Oncologico M. D. Anderson International Spain, Madrid, Spain; Vall d'Hebron Institute of Oncology, Barcelona, Spain

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Abstract Disclosures


Background: PM01183 is a new anticancer agent that blocks the trans-activated transcription and induces the formation of double-strand breaks in a wide range of cancer cell lines, including platinum-resistant (Pt-res). Methods: PRROC patients (pts) with less than 3 prior chemotherapy (CT) containing lines, adequate organ function and performance status (PS) 0-2 were included. The primary endpoint was overall response rate (ORR) (by RECIST v1.1 and/or Rustin criteria). Secondary endpoints were progression free survival (PFS), overall survival (OS) and safety. Pts were treated with i.v. PM01183 (P1), 7 mg flat dose, q3wk in the first stage. In the second stage, pts were randomized (1:1) to PM01183 (P2) or topotecan (T) (standard or weekly regimen). Cross-over to the P2 arm was allowed after progression to T. Results: 81 pts were included (P1/P2/T: 22/30/29). Global median characteristics of pts were balanced: age 61 years; PS 1; Pt-res (P1/P2/T: 16/17/16 pts); prior bevacizumab: 18.5% of pts, median prior advanced chemotherapy lines: 1 in each arm. Efficacy results are summarized in the Table. The most common PM01183 related AEs were neutropenia (Gr 3-4, 85%), febrile neutropenia (23%), thrombocytopenia (Gr 3-4, 29%), nausea/vomiting (Gr 3, 16%) and fatigue (Gr 3, 37%) Conclusions: PM01183 is an active drug in Pt-res/Pt-ref ovarian cancer. The study has met the primary endpoint, showing statistically significant superiority over T in terms of ORR, PFS and OS. The safety profile is predictable and manageable; prophylactic G CSF is recommended. A phase III study in Pt-res ovarian cancer is planned.

First stage
Second stage
OR [n (%)]
CR 0 (0) 1 (3) 0 (0) -
PR §6 (27) 4 (14) 0 (0)
SD 12 (55) 13 (45) 15 (52)
PD 4 (18) 10 (34) 14 (48)
Treatment failure 0 (0) 1 (3) 0 (0)
ORR (%) (95% CI) 22 (11-35) - 0.006
Pt-res 30 (16-49) - 0.002
Pt-ref 6 (0-27) - 1   
DCR (%) 71 52 -
PFS (months) * 3.9 2.0 0.003
Pt-res 4.5 7.1 1.7 0.002
Pt-ref 2.9 1.4 2.7 0.809
OS (months) + 10.6 5.7 0.029
Pt-res 12.6 Not reached 7.0 0.053
Pt-ref 12.6 8.7 5.4 0.253

Abbreviations: Pt-ref, platinum-refractory; DCR, disease control rate. §2 PRs by Rustin criteria, *events: 81%; +events: 64%.