Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

Abstract

Background: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer.

Methods: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016).

Results: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met.

Conclusions: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

Fig. 1

Patient disposition. *One patient was randomly assigned to the placebo group but withdrew consent and withdrew from the study without receiving treatment. This patient subsequently died but is not included in the number of deaths for patients who discontinued the study after being treated with placebo

Fig. 2

Overall survival in all patients and according to BRCA mutation status: a overall study population; b BRCAm subgroup; c BRCAwt subgroup

Fig. 3

Duration of exposure to treatment. *Patient numbers are shown on the chart. ^†Ten patients had an unknown BRCAm status

Fig. 4

Characterisation of common AEs: time to first event (Event rate = number of first events/exposure during time interval. Note that y axes scales are different between parts a, b, c and d) of a nausea, b vomiting, c fatigue/asthenia and d anaemia^†, and prevalence by month and grade of e nausea, f vomiting, g fatigue/asthenia and h anaemia^† in olaparib-treated patients. ^†Includes patients with anaemia, haemoglobin decreased, red blood cell count decreased and haematocrit decreased