Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer
Mené sur 52 puis 29 patientes atteintes d'un cancer épithélial de l'ovaire réfractaire et/ou résistant au cisplatine, cet essai de phase II compare l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un composé appelé PM01183 et du topotécan
Background: PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer. Patients and methods: Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was objective response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n=22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every three weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on Days 1–5 q3wk or weekly (every four weeks, q4wk) Results: ORR was 23% (95%CI, 13–37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95%CI, 2.5–6.9 months), and 23% (95%CI, 0–51%) of responses lasted six months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease (ORR=30% [95%CI, 16–49%]; For the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95%CI, 2.7–5.6), and 5.0 months (95%CI, 2.7–6.9) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85%; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183. Conclusion: PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (4.0 mg/m2).