OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer

Abstract

Background In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now report the planned final overall survival (OS) results, and describe the most common adverse events (AEs) to better understand olaparib tolerability in this population. Patients and methods OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300 mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points. Results A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 17.1 months with TPC (HR 0.90, 95% CI 0.66–1.23; P = 0.513); median follow-up was 25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29–0.90; yes (second/third-line): 1.13, 0.79–1.64]; receptor status (triple negative: 0.93, 0.62–1.43; hormone receptor positive: 0.86, 0.55–1.36); prior platinum (yes: 0.83, 0.49–1.45; no: 0.91, 0.64–1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure. Conclusions While there was no statistically significant improvement in OS with olaparib compared to TPC, there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with no evidence of cumulative toxicity during extended exposure.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

“…The median OS with olaparib compared with treatment of physician's choice was 19.3 months versus 17.1 months, respectively (HR, 0.90; 95% CI, 0.66-1.23; P5.513). 113 QOL was significantly better in the olaparib arm. It is interesting to note that patients who had not received prior chemotherapy in the metastatic setting achieved a 7.9-month longer median OS compared with treatment of physician's choice.…”

“…It is interesting to note that patients who had not received prior chemotherapy in the metastatic setting achieved a 7.9-month longer median OS compared with treatment of physician's choice. 113 In the phase III EMBRACA trial, patients with advanced breast cancer harboring the germline BRCA mutations to a PARP inhibitor were randomized to talazoparib (n5287) or to physicians choice of single-agent chemotherapy (n5144). 114 The median PFS among patients in the talazoparib group was longer than the control group (8.6 months [95% CI, 7.2-9.3] vs 5.6 months [95% CI, 4.2-6.7]; HR for disease progression or death, 0.54; 95% CI, 0.41 to 0.71; P,.001).…”

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

“…During the last years, new drugs such as the Poly(ADP-ribose) polymerase (PARP)-inhibitors targeting HRR-defective tumors were studied in several clinical trials. Two different phase III trials (OlympiaAD and EMBRACA) showed an improved response rate and PFS for PARP inhibitor (Olaparib or Talazoparib)-treated patients compared to patients who received standard chemotherapy [10,11]. Among the new therapeutics Eribulin, a non-taxane microtubule inhibitor, demonstrated an improved overall survival (OS) in patients with MBC already treated with taxane and anthracycline compared to treatment with physicians' choice in the EMBRACE trial [12].…”

Hype or hope? The strange case of platinum salts’ renaissance in breast cancer

“…Beyond chemotherapy, the use of first-line single-agent PARP-inhibitors might be an option, based on the intriguing ORR and PFS results observed in phase 3 OLYMPIAD and EMBRACA trials [15][16][17]. Furthermore, hormonal therapy might be still appropriate in hormone-receptor-positive BRCA1/2 mutated BC diseases without visceral crisis.…”