ASTRAZENECA PHARMACEUTICALS LP: Updated overall survival data for Lynparza in BRCA-mutated HER2-negative metastatic breast cancer presented at AACR

AstraZeneca Pharmaceuticals LP issued the following announcement on April 15.

The trial compared Lynparza with chemotherapy (physician’s choice of capecitabine, eribulin or vinorelbine) for patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer and met its primary endpoint of progression-free survival (PFS).

Results at AACR include updated findings from the secondary endpoint of overall survival (OS). While the trial was not powered to demonstrate a statistically-significant difference, the median OS was 19.3 months in patients treated withLynparza and 17.1 months for patients treated with chemotherapy (HR 0.90; 95% CI 0.66-1.23; p=0.513). At the final OS data cut-off (64% maturity), nearly 13% of patients remained on Lynparza and no patients remained on chemotherapy.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “OlympiAD is the first Phase III trial to demonstrate disease control with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer. While the trial was not powered to show overall survival compared to chemotherapy, the results are another encouraging marker in the use of Lynparza for this patient population.”

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “For patients and physicians, these results are meaningful in that they support the progression-free survival endpoint – which showed that patients treated with Lynparza gained seven months chemotherapy-free time – and reinforce the importance of identifying BRCA status to optimise metastatic breast cancer management.”

When analysing the predefined subgroups, the results were consistent with the overall analysis, which did not show a statistically-significant difference between arms. The greatest difference was seen in patients who had not received chemotherapy in the metastatic setting with a median difference in OS of 7.9 months with Lynparza (HR 0.51; 95% CI 0.29-0.90; nominal p=0.02; median 22.6 vs 14.7 months).

Table 1: Predefined subgroups for OS analysis

The safety profile of Lynparza remained consistent with the primary analysis, indicating no relevant cumulative toxicity with extended exposure. Serious adverse events (Grade >3) were reported in 38% of patients who received Lynparza vs 49.5% of patients in the chemotherapy arm.

These results build on previously reported findings, which demonstrated Lynparza significantly improved PFS (HR 0.58; 95% CI 0.43-0.80; p=0.0009 median 7.0 vs 4.2 months) and showed benefit beyond initial disease progression, prolonging time to second progression or death (PFS2) by 3.9 months (HR 0.57; 95% CI 0.40-0.83; p=0.003 median 13.2 months vs 9.3 months). Previously reported findings also showed Lynparza doubled objective response rates (52% [95% CI 44-60] vs 23% [95% CI 13-35]) and improved quality-of-life scores. The data from the OlympiAD trial can be found in the 10 August 2017 issue of the New England Journal of Medicine.

In January 2018, Lynparza was approved by the US FDA for the treatment of metastatic breast cancer, based on the OlympiAD data. A Type II variation application was recently validated by the European Medicines Agency for Lynparza in gBRCAm HER2-negative metastatic breast cancer.

A Phase III trial (n=1800), OlympiA, is evaluating Lynparza as an adjuvant treatment in patients with gBRCA HER2-negative breast cancer, with results expected in 2020. The trial is powered to assess potential benefit in OS.

Lynparza is approved in around 60 countries for advanced ovarian cancer and has treated more than 20,000 patients globally. It has the broadest clinical development programme of any PARP inhibitor and AstraZeneca and MSD are working together to bring Lynparza to more patients across multiple cancers.

Original source can be found here.