968O - Lurbinectedin (PM01183) activity in platinum-resistant/refractory ovarian cancer patients. Preliminary results of an ongoing two-stage Phase II study.

Date 30 September 2012
Event ESMO Congress 2012
Session Gynecological cancer
Topics Cytotoxic agents
Ovarian Cancer
Therapy
Biological therapy
Presenter Dominique Berton-Rigaud
Authors D. Berton-Rigaud1, J. Alexandre2, M. Provansal3, A. Casado4, A. Gonzalez Martin5, C. Fernández6, C. Kahatt6, S. Szyldergemajn6, J.M. Del Campo7, A.M. Poveda8, E.M. Guerra9, I.L. Ray-Coquard10
  • 1Oncology, Centre René Gaducheau, Nantes/FR
  • 2Oncology, Hôtel Dieu, Paris/FR
  • 3Oncology, Institut Paoli Calmettes, Marseille/FR
  • 4Oncology, Hospital Clinico Universitario San Carlos, Madrid/ES
  • 5Servicio De Oncologia Medica, Hospital Clinico Universitario San Carlos, Madrid/ES
  • 6Clinical Oncology, PharmaMar, Colmenar Viejo, Madrid/ES
  • 7Oncology, Hospital Universitario Vall d’Hebron, Barcelona/ES
  • 8Oncologia, Instituto Valenciano de Oncologia, ES-46009 - Valencia/ES
  • 9Oncology, Hospital Ramón y Cajal, Madrid/ES
  • 10Oncology, Centre Leon Berard, Lyon/FR

 

Abstract

Background: PM01183 is a new anticancer agent, acting through minor groove DNA-binding against a wide range of ovarian cancer cell lines and orthotopic models, including several platinum-resistant. The first step of a randomized phase II trial is reported here.

Methods: Between Dec11 and Feb12, 22 platinum-resistant or refractory ovarian cancer patients (pts) with less than 3 prior chemotherapy (CT) lines for advanced disease, adequate major organ function and performance status (ECOG) 0-2 were included in the exploratory first stage of this study. The primary endpoint was confirmed response rate (either by RECIST v1.1 or by Rustin criteria). At least two confirmed responses (by either criterion) were required to proceed to the second stage. This study was reviewed and approved by each institutional IRBs and ECs, as well as by the Spanish and French health authorities.

Results: Median age was 59 years (35–77), median ECOG was 1 (0-2).15 (68%) and 7 (32%) pts received 1 or 2 prior CT lines for advanced disease, respectively. Six pts were platinum-refractory (no response to last platinum-containing CT) and 16 were platinum-resistant (platinum-free interval < 6 months). All patients (n=22) were evaluable for efficacy. 6 pts responded (two by Rustin and four by RECIST) for an ORR: 27% (95%CI: 11%-50%) with 1 radiological CR. Only six patients (27%) had progressed at the first evaluation. Thus, overall disease control rate was 73%. As most patients are still ongoing, it is therefore too early to evaluate both quality and/or duration of response. The preliminary toxicity profile observed confirms prior phase I results, with myelosuppression, nausea/vomiting despite adequate prophylaxis, and fatigue being the most common drug-related toxicity. No drug related deaths have been reported.

Conclusions: PM01183 is tolerable and has a very promising activity in platinum-resistant/refractory ovarian cancer patients. The second stage started in Apr 2012 and 60 additional patients will be randomized to PM01183 or topotecan, in order to confirm the initial results. Updated results will be presented during the meeting.