The efficacy of Lynparza was evaluated in OlympiA (NCT02032823), a randomized (1:1), double-blind, placebo-controlled, international study in patients with gBRCAm HER2-negative high risk early breast cancer who had completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomized to receive Lynparza tablets 300 mg orally twice daily or placebo. Treatment was continued for up to 1 year, or until disease recurrence, or unacceptable toxicity. Patients were required to have completed at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or both. Prior platinum for previous cancer (e.g., ovarian) or as adjuvant or neoadjuvant treatment for breast cancer was allowed. Patients with high-risk early breast cancer were defined as follows:

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    patients who received prior neoadjuvant chemotherapy: patients with either triple negative breast cancer (TNBC) or hormone receptor positive breast cancer must have had residual invasive cancer in the breast and/or the resected lymph nodes (non-pathologic complete response) at the time of surgery. Additionally, patients with hormone receptor positive breast cancer must have had a score of ≥3 based on pre-treatment clinical and post-treatment pathologic stage (CPS), estrogen receptor (ER) status, and histologic grade as shown in Table 21.

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    patients who received prior adjuvant chemotherapy: patients with TNBC must have had node positive disease or node negative disease with a ≥2cm primary tumor; patients with hormone receptor positive, HER2-negative breast cancer must have had ≥4 pathologically confirmed positive lymph nodes.

Randomization was stratified by hormone receptor status (hormone receptor positive versus triple negative), by prior neoadjuvant versus adjuvant chemotherapy, and by prior platinum use for breast cancer (yes versus no).

The major efficacy outcome measure was invasive disease free survival (IDFS), defined as the time from randomization to date of first recurrence, where recurrence is defined as invasive loco-regional, distant recurrence, contralateral invasive breast cancer, new cancer or death from any cause. An additional efficacy outcome measure was OS. 

A total of 1836 patients were randomized, 921 to Lynparza and 915 to placebo. Demographic and baseline characteristics were well balanced between arms. The median age was 42 years. Sixty-seven percent (67%) of patients were White, 29% were Asian, and 3% were Black. Three percent (3%) of patients were Hispanic or Latino. Two patients (0.2%) in the Lynparza arm and four patients (0.4%) in the placebo arm were male. Sixty-one percent (61%) of patients were pre-menopausal. Eighty-nine percent (89%) of patients were ECOG performance status 0 and 11% ECOG PS 1. Eighty-two percent (82%) of patients had TNBC and 18% had hormone receptor-positive disease. Fifty percent (50%) of patients had received prior neoadjuvant and 50% received prior adjuvant chemotherapy. Ninety-four percent (94%) of patients received anthracycline and taxane chemotherapy. Twenty-six (26%) of patients overall had received prior platinum for breast cancer. Ninety percent (90%) of patients with hormone receptor positive breast cancer received concurrent endocrine therapy.

Patients enrolled based on local gBRCA test results provided a sample for retrospective confirmatory central testing with BRACAnalysis®. Out of 1836 patients enrolled into OlympiA, 1623 were confirmed as gBRCAm by Myriad BRACAnalysis®, either prospectively or retrospectively. 

A statistically significant improvement in IDFS and OS was demonstrated in patients in the Lynparza arm compared with the placebo arm. Efficacy data for OlympiA (FAS) are presented in Table 22 and Figures 6 and 7.

Figure 6 Kaplan-Meier Curves of IDFS – OlympiA

Figure 7 Kaplan-Meier Curves of OS – OlympiA