The combination of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and durvalumab has been studied in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer. However, this phase 2 study (MEDIOLA) aimed to evaluate the safety and efficacy of the combination of olaparib and durvalumab (double cohort) as well as the combination of olaparib and durvalumab plus bevacizumab in patients with non-germline BRCA-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer.
In this study, patients with confirmed non-gBRCAm platinum-sensitive relapsed ovarian cancer whose disease had progressed after 1 to 2 lines of prior platinum-based chemotherapy received olaparib 300 mg twice daily and durvalumab 1.5 g intravenously every 4 weeks (n = 32). An additional cohort of patients received the same therapies with the addition of bevacizumab 10 mg/kg every 2 weeks (n = 31). Patients were treated until disease progression. Tumors were assessed at baseline and every 8 weeks by RECIST v1.1. The primary end points for this study included 24-week disease control rate (DCR) and safety; furthermore, secondary end points including objective response rate (ORR), median duration of response (DOR), and progression-free survival (PFS) were also assessed.
At the data cutoff for this analysis, 22% of the 31 enrolled patients receiving olaparib and durvalumab and 42% of the 32 enrolled patients receiving olaparib and durvalumab plus bevacizumab were still on treatment. Two (6%) patients who received olaparib and durvalumab and 5 (16%) patients who received olaparib and durvalumab plus bevacizumab discontinued ≥1 study drugs due to an adverse event. The most common adverse events of grade ≥3 in the olaparib and durvalumab cohort were anemia, lipase increased, and neutropenia, whereas in the olaparib and durvalumab plus bevacizumab cohort, anemia, hypertension, fatigue, lipase increased, and decreased white blood cell count were most common.
The 24-week DCR was 28.1% (90% confidence interval [CI], 15.5-43.9) for the olaparib and durvalumab cohort and 77.4% (90% CI, 61.7-88.9) for the olaparib and durvalumab plus bevacizumab cohort. For the olaparib and durvalumab cohort, ORR was 34.4% (95% CI, 18.6-53.2), median DOR was 6.9 months (interquartile range, 5.4-11.1), and median PFS was 5.5 months (95% CI, 3.6-7.5). For the olaparib and durvalumab plus bevacizumab cohort, ORR was 87.1% (95% CI, 70.2-96.4), median DOR was 11.1 months (interquartile range, 7.4-16.4), and median PFS was 14.7 months (95% CI, 10.0-18.1). High response rates for the olaparib and durvalumab plus bevacizumab cohort were consistent across subgroups based on genomic instability status.
Both medication combinations were well tolerated in this patient population, and the safety profiles were consistent with previously reported safety profiles for these agents. Although the olaparib and durvalumab combination did not meet the prespecified target for DCR of 80%, the 95% CI for the olaparib and durvalumab plus bevacizumab combination did include the target value. The primary and secondary end point outcomes for the olaparib and durvalumab plus bevacizumab combination show promising interim results for this patient population and warrant further investigation.
Abstract and Oral Presentation 814MO. ESMO 2020. September 19-21, 2020. Phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC).