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Response to Olaparib Monotherapy in Relapsed Ovarian Cancer by HRR Gene Mutational Status and HRD Scarring Analysis

Conference Correspondent  - ESMO Highlights

The CLIO study is a phase 2 randomized, open-label, interventional study of patients with relapsed epithelial ovarian cancer on olaparib monotherapy compared with standard-of-care chemotherapy. Patients included in the study had measurable, recurrent disease and had undergone at least 1 previous course of platinum-based chemotherapy. The primary outcome was overall response rate (ORR), as defined by RECIST criteria, in patients with platinum-resistant ovarian cancer (PROC) and platinum-sensitive ovarian cancer (PSOC); this was further analyzed in relation to the presence of homologous recombination repair (HRR) deficiency (HRD). The investigators utilized formalin-fixed paraffin-embedded samples of the primary tumor to identify somatic HRR mutations with the SureMASTR assay. HRD scarring analysis was completed using an amplicon-based sequencing assay.

The study included 60 patients with PSOC and 100 with PROC who were randomized in a 2:1 ratio to the olaparib arm (n = 107) or the chemotherapy arm (n = 53). Patients received olaparib 300 mg twice daily or the physician’s choice of chemotherapy regimen (PSOC: carboplatin + gemcitabine, carboplatin + paclitaxel, carboplatin + liposomal doxorubicin; PROC: doxorubicin 4-weekly, topotecan, or paclitaxel weekly). The median number of previous lines of treatment was 3, ranging from 1 to 9. Approximately 5% of patients had been previously treated with a poly (ADP-ribose) polymerase (PARP) inhibitor and nearly 50% had been previously treated with bevacizumab.

Because of disease progression, 44 patients in the chemotherapy arm crossed over to the olaparib arm, increasing the number of patients on that arm to 151 (median follow-up, 28.2 months). Among all patients who received olaparib, the confirmed ORR was 17.6%. The confirmed ORR among patients with PROC (n = 105) and PSOC (n = 46) was 10.9% and 31.8%, respectively. Of the 130 patients who were BRCA wild-type, 18% met the response criteria; the ORR among PROC and PSOC was 10% (9/89) and 34% (14/41), respectively. The confirmed ORR in patients with BRCA1 mutations (n = 17) and BRCA2 mutations (n = 5) was 41.2% and 20%, respectively. There were 27 patients with HRR mutations, and 33% responded to treatment. Of these 27 patients, 21 (77.8%) patients had PROC and 6 (22.2%) patients had PSOC with response rates of 24% and 67%, respectively. Of the 124 patients who were HRR wild-type, 19% (23/124) responded to olaparib. Of these patients, 84 (67.8%) had PROC and 40 (32.2%) had PSOC with response rates of 11% and 35%, respectively. Among 69 HRD-positive patients, the ORR was 27.5%; 45 (65.2%) of these patients had PROC and 24 (34.8%) had PSOC, and ORRs were 15.6% and 50%, respectively. Among 60 HRD-negative patients, the ORR was 6.7%; 40 (66.7%) of these patients had PROC and 20 (33.3%) had PSOC, and ORRs were 5% and 10%, respectively.

The median progression-free survival in olaparib-treated patients was 4.8 months; 7.6 months for PSOC and 2.8 months for PROC, and 7.4 months for patients with HRR mutations and 2.9 months for those with HRR wild-type.

The authors concluded that similar efficacy was observed between olaparib and standard-of-care chemotherapy in patients with relapsed epithelial ovarian cancer, and that although BRCA mutations predicted response to olaparib, other HRR mutations were less predictive.

Reference

Abstract and Poster 817P. ESMO 2020. September 19-21, 2020. Response to olaparib monotherapy in relapsed ovarian cancer by HRR gene mutational status and HRD scarring analysis: results from the randomized phase II CLIO trial.

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