Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multi-study analysis of response rates and safety
A partir de données portant sur 300 patientes avec mutations constitutionnelles BRCA1/2, atteintes d'un cancer récidivant de l'ovaire et ayant été incluses dans 2 essais de phase I et 4 essais de phase II, cette étude évalue l'efficacité, du point de vue du taux de réponse objective et de la durée de la réponse, et la toxicité de l'olaparib après trois lignes de chimiothérapie
Background The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. Patients and methods This analysis evaluated pooled data from two Phase I trials (NCT00516373 [Study 2]; NCT00777582 [Study 24]) and four Phase II trials (NCT00494442 [Study 9]; NCT00628251 [Study 12]; NCT00679783 [Study 20]; NCT01078662 [Study 42]) that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline. Results Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% (95% CI: 30, 42) and the median DoR was 7.4 months (95% CI: 5.7, 9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI: 25, 38), with a DoR of 7.8 months (95% CI: 5.6, 9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively. Conclusion Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy. Clinical trial numbers ClinicalTrials.gov, NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662