OlympiAD Trial Shows Efficacy of Olaparib in Women with HER2-Negative Metastatic Breast Cancer and a Germline BRCA Mutation

Olaparib is a poly (ADP-ribose) polymerase inhibitor that has already received FDA approval for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, and for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy.¹

OlympiAD was a randomized, open-label, phase 3 trial that enrolled 302 patients with HER2-negative metastatic breast cancer (MBC) with a germline BRCA1 or BRCA2 mutation, either hormone receptor (HR)-positive or triple negative.² All patients had received ≤2 prior rounds of anthracycline- or taxane-based chemotherapy for MBC, and those with HR-positive disease had received hormonal therapy. They were randomized in a 2:1 ratio to olaparib tablets, 300 mg twice daily, or single-agent chemotherapy (21-day cycles of either capecitabine, vinorelbine, or eribulin) at the treating physician’s discretion. Because olaparib tablets were used in this study, the dosage of olaparib that patients received was different from the FDA-approved dosage of 400 mg twice daily in capsular formulation for the treatment of BRCA-mutated ovarian cancer. Treatment continued until disease progression was confirmed by independent review or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS).²

Results of this study were recently published in The New England Journal of Medicine.² As reported by Robson and colleagues, median PFS was 7.0 months in the olaparib arm compared with 4.2 months in the chemotherapy arm (hazard ratio, 0.58; P = .001). The median time from randomization to second progression or death was 13.2 months versus 9.3 months in the olaparib and chemotherapy arms, respectively (hazard ratio, 0.57; P = .003).

Additionally, the safety profile of olaparib was favorable. The rate of grade ≥3 adverse events was lower in the olaparib arm than in the standard chemotherapy arm (36.6% vs 50.5%), as were the percentage of patients who discontinued treatment  because of adverse events (4.9% vs 7.7%) and the percentage who had adverse events leading to dose reductions (25.4% vs 30.8%).²

More than 30 trials evaluating the use of olaparib in various breast cancer subpopulations are underway.

The ongoing randomized REVIVAL trial is comprised of 2 parts. In part 1, investigators will determine the maximum tolerated dose of 2 cycles of carboplatin plus olaparib and 1 cycle of olaparib monotherapy in patients with advanced breast cancer. In part 2, patients with BRCA1- or BRCA2-mutated HER2-negative breast cancer will be randomized to 2 cycles of carboplatin plus olaparib followed by olaparib monotherapy (dosed according to the study results of part 1) or capecitabine.³

In the multicenter DORA trial, which recently began enrolling patients, investigators will evaluate the efficacy of olaparib monotherapy and olaparib plus durvalumab as maintenance therapy in patients with advanced triple-negative breast cancer who were previously treated with platinum-based therapy.⁴

As data from these ongoing trials become available, the clinical utility of olaparib in a variety of breast cancer subtypes will be better established.

References

1. Lynparza (olaparib) tablets [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2017.

2. Robson M, Im S-A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377:523-533.

3. Schouten PC, Dackus GMHE, Marchetti S, et al. A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial. Trials. 2016;17:293-301.

4. ClinicalTrials.gov. Phase II Multicenter Study of Durvalumab and Olaparib in Platinum Treated Advanced Triple Negative Breast Cancer (DORA). NCT03167619.