In this study, researchers explored whether there is a potential synergistic effect of olaparib when combined with pegylated liposomal doxorubicin, highlighting a potential means to improve tolerability.
During a poster presentation at the European Society for Medical Oncology Virtual Congress 2020, José Alejandro Pérez Fidalgo, MD, PhD, Medical Oncologist, Gynecological and Sarcoma Unit, INCLIVA University Hospital of Valencia, Valencia, Spain, discussed the benefit of olaparib in patients with platinum-resistant ovarian cancer with BRCA wild-type tumors. The premise of this study is that the activity of olaparib may be improved with the DNA-damaging effect of chemotherapy through a synergistic effect.
The original study design of the phase 2 trial was earlier discussed and published by Pérez Fidalgo and colleagues in January 2019 when 16 patients had been recruited.1
Irrespective of BRCA status, patients with high-grade serous or endometrioid cancer and 1 previous platinum-resistant ovarian cancer (between 28 days to 6 months after last platinum therapy) were eligible for participation in the study. Patients who had received ≤4 previous lines (≤5 in patients with BRCA-mutation disease) and primary platinum-resistant ovarian cancer were only allowed in the presence of BRCA mutation, otherwise ≥1 previous platinum-sensitive relapses were required. The primary end point of the study was progression-free survival (PFS) at 6 months defined by Response Evaluation Criteria in Solid Tumors version 1.1, and the threshold for futility was defined as 40% PFS at 6 months.
Patients received 6 cycles of olaparib at 300 mg twice daily in addition to pegylated liposomal doxorubicin at 40 mg/m2 intravenously every 28 days, followed by 300 mg olaparib twice daily until toxicity or disease progression. A protocol amendment was enacted due to high toxicity reports, reducing the dose of pegylated liposomal doxorubicin to 30 mg/m2.
Thirty-one patients received ≥1 cycles in the intent-to-treat cohort, in which the median age was approximately 58.03 years, Eastern Cooperative Oncology Group (ECOG) performance status of 1 was 67.7%, and serous subtype 84%. Twenty patients were included in the per-protocol cohort, in which the median age was 60 years, ECOG performance status of 1 was 75%, serous subtype was 85%, and wild-type BRCA status was 75%, mutant BRCA status 20%, and unknown 5%.
In the per-protocol cohort, the 6-month PFS was 46.1% (95% confidence interval, 27.2-78.3), with a median PFS of 5.42 months (range, 4-12 months). Remarkably, the overall control rate was 90%, with 65% of patients attaining stable disease, and 25% reaching partial response.
In the intent-to-treat population, grade ≥3 adverse events (AEs) were reported by 74% of patients, with the most frequent being neutropenia (39%), anemia (19%), and febrile neutropenia (10%). Serious AEs were less frequent (21%) in the reduced dose of pegylated liposomal doxorubicin cohort (30 mg/m2) when compared with the 47% of patients receiving the larger dose of pegylated liposomal doxorubicin (40 mg/m2).
The authors concluded that regardless of BRCA status, olaparib combined with pegylated liposomal doxorubicin demonstrated clear activity with 46% of patients with a 6-month PFS rate in platinum-resistant ovarian cancer patients. Furthermore, and perhaps importantly, the study showed that pegylated liposomal doxorubicin at 30 mg/m2 in the combination was more tolerable.
Source: Pérez Fidalgo JA, et al. Ann Oncol. 2020;31(4_suppl). Abstract 832P.
1. Pérez Fidalgo JA, Iglesia M, Bohn U, et al. GEICO1601-ROLANDO: a multicentric single arm phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer. Future Sci OA. 2019;5:FSO370.