Progression-free survival (PFS), clinical benefit, time to first subsequent therapy (TFST), and overall survival (OS) were similar between patients administered olaparib monotherapy and those receiving chemotherapy in a population of patients with recurrent germline BRCA wild-type platinum-sensitive epithelial ovarian cancer. Objective response rate (ORR) tended to be lower in patients receiving olaparib, but this difference was not significant. These findings come from the randomized phase 2 CLIO study, presented by Liselore Loverix, MD, from the Department of Gynecological Oncology at KU Leuven University Hospitals in Leuven, Belgium, at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.
The CLIO trial evaluated olaparib single-agent therapy versus standard-of-care chemotherapy in patients with measurable disease who relapsed after at least 1 prior line of platinum-based chemotherapy. Patients were divided into 2 groups: platinum-sensitive patients who relapsed ≥6 months after platinum-based chemotherapy, excluding patients with known germline or somatic BRCA mutations (n = 60); or platinum-resistant patients who relapsed <6 months after platinum-based chemotherapy, excluding primary platinum-refractory disease (ie, relapse during or <28 days after first-line platinum), and including patients with germline or somatic BRCA mutations (n = 100).
The primary end point of the study was objective response in all patients receiving olaparib monotherapy with homologous recombination repair (HRR)-deficient versus HRR-proficient tumors. At SGO, Dr Loverix discussed only the secondary end points of ORR, PFS, OS, clinical benefit rate at 12 weeks, and duration of clinical benefit for patients in the platinum-sensitive recurrent ovarian cancer (PSOC) cohort treated with olaparib monotherapy versus chemotherapy, as well as the hereditary breast and ovarian cancer (HBOC) mutational analysis performed.
Patients were randomized 2:1 to olaparib oral monotherapy at a dose of 300 mg twice daily (n = 40) or physician’s choice of chemotherapy (n = 20). Patients in the chemotherapy arm were allowed to cross over at the time of progressive disease and receive the poly (ADP-ribose) polymerase (PARP) inhibitor as subsequent therapy. Prior bevacizumab was allowed (approximately 50% for both groups), and baseline characteristics were well-balanced between study arms.
Study recruitment was completed in the beginning of 2019, and until now, median follow-up for PSOC patients is 26 months, she noted. Median months since diagnosis was 34 versus 43 in the olaparib and chemotherapy groups, respectively. Median prior lines of therapy were 2 for both groups.
The ORR was lower in olaparib-treated patients, although no significant difference was observed. ORR was 37.5% (15/40) in patients who received olaparib monotherapy, and 65% (13/20) in patients on chemotherapy (P = .06).
“At 12 weeks after the start of therapy, partial response or stable disease was seen in 80% of olaparib patients versus 85% of chemotherapy patients,” Dr Loverix reported. “So at 12 weeks, the clinical benefit remains equal to us.”
PFS, OS, and TFST were all similar between treatment arms. Median PFS was 6.5 months with olaparib and 8.8 months with chemotherapy, and median OS was 31.2 months versus 23.9 months for olaparib and chemotherapy, respectively. TFST was 9 months for both groups. No new safety signals were identified in either study arm.
All patients in this platinum-sensitive group were BRCA wild-type, and all patients underwent germline HBOC gene panel screening (including BRCA1, BRCA2, RAD51C, RAD51D, and BRIP1), as well as somatic HRR gene mutation testing.
Post-hoc HBOC/HRR mutational analysis was presented, and 6 of 7 HBOC/HRR-mutated patients responded to olaparib or chemotherapy.
“Interestingly, looking at the overall response rate of the olaparib group, 2 of 3 HRR gene-mutated patients responded well,” she said. “In the chemotherapy group, this was even 100%.”
Full homologous recombination deficiency testing is ongoing and will be presented at a later date.
- SGO 2020 Annual Meeting on Women’s Cancer. Abstract 30. Presented May 7, 2020.