At a virtual press briefing ahead of the 2021 American Society of Clinical Oncology annual meeting, researchers reported clinically significant benefit 1 year after starting standard treatments, such as surgery, chemotherapy, hormone therapy or radiotherapy, in patients with early BRCA1 / 2 -mutant HER2-negative breast cancer at high risk of recurrence.
“The OlympiA study is the first to report the benefits of [an adjuvant] PARP inhibitor for early forms of germline cancer associated with the BRCA1 / 2 mutation, ”said study author Andrew Tutt, PhD, MB ChB, Head of Breast Cancer Research Division and Director from the Breast Cancer Now Toby Robins Research Center at the Institute of Cancer Research and Guy’s Hospital King’s College, London, UK, a Clinical Investigator in the Clinical and Laboratory Trials Program and a Consultant Clinical Oncologist. “Patients who received olaparib after surgery and chemotherapy were more likely to be alive without cancer,” [as well as] avoid metastasis, as patients who received placebo.
Patients with early HER2-negative breast cancer who carry a BRCA1 / 2 mutation, which is present in about 5% of all breast cancers, are at high risk of the disease coming back. Although the results have been positive for patients with these mutations who have received standard treatments such as surgery, radiation therapy and chemotherapy, the risk of recurrence remains high for some patients. As such, additional new targeted therapies are needed to reduce the risk of recurrence in this patient population.
Olaparib is a PARP inhibitor that targets DNA repair defects in certain mutant germline cancers and was previously approved by the FDA in January 2018 for the treatment of patients with BRCA- germline metastatic breast cancer. positive and HER2-negative. As such, the researchers sought to examine the agent in patients with early HER2-negative breast cancer with germline BRCA mutation.
The trial included 1,836 patients with HER2-negative breast cancer carrying a BRCA germline mutation who were randomized 1: 1 to receive either 300 mg of oral olaparib (n = 921) twice per day for 1 year, i.e. a placebo (n = 915). In addition, patients had to have been treated for early stage breast cancer (stage II-III) and have completed surgery and chemotherapy, with or without radiation therapy. The inclusion criteria also required that patients were at high risk of disease recurrence. Those who had received previous treatment with a PARP inhibitor were not eligible to enroll.
The primary endpoint of the study was iDFS; secondary endpoints included distant disease-free survival (DDFS), overall survival (OS), health-related quality of life and safety. “Strict criteria were applied for a planned interim analysis,” Tutt said. “During this analysis, OlympiA’s independent data monitoring committee found [that] these strict criteria were met for the first reports.
Additional results indicated that after a median follow-up of 2.5 years, patients treated with olaparib experienced a 43% reduction in DDFS, including metastatic disease, new cancer, and death in any case. or the cause (RR: 0.57; 99.5% CI, 0.39-0.83; P
At the time of the first primary endpoint report, OS data were considered immature. However, although fewer deaths were reported in patients receiving olaparib compared to placebo, OS was not significantly different between the 2 study cohorts at a median follow-up of 2.5 years (RR: 0.68; 99% CI: 0.44-1.05; P = 0.024). In addition, the difference in OS rate at 3 years between the 2 arms was 3.7% (95% CI: 0.3% to 7.1%).
In terms of safety profile, the adverse reactions (AEs) reported in the olaparib group were consistent with what had previously been reported with the agent. In addition, olaparib did not increase serious side effects, including hospitalizations or the occurrence of other cancers such as leukemia. However, Grade 3 or greater AEs were reported more often in patients receiving olaparib therapy, and included anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue ( 2%).
The most common AEs, regardless of grade, reported in patients who received olaparib included nausea (57%), fatigue (40%), anemia (23%), vomiting (23%) ) and headaches (20%). In addition, the most common adverse reactions of any grade in the placebo arm were fatigue (27%), nausea (23%), headache (17%), diarrhea (14%), and arthralgia. (12%).