The use of the PARP inhibitor olaparib (Lynparza) for 1 year after receiving standard chemotherapy in the neoadjuvant or the adjuvant setting significantly improved invasive disease-free survival in patients with high-risk, early-stage, HER2-negative breast cancer and BRCA1 or BRCA2 mutations, according to results presented at the American Society of Clinical Oncology 2021 virtual meeting.
An interim analysis of the OlympiA clinical trial showed that after an average follow-up of 2.5 years, 77.1% of the patients who received standard chemotherapy plus placebo had an estimated 3-year survival without invasive disease. However, this rate increased to 85.9% of patients without invasive disease with the addition of olaparib therapy for 1 year.
These results were presented by lead investigator Andrew Tutt, MBChB, PhD, Director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research and Guy’s Hospital in London, England.
“The OlympiA study results, the first reporting the effects of a PARP inhibitor as an adjuvant therapy on survival end points, suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation-associated early breast cancer who have levels of recurrence risk requiring neoadjuvant or adjuvant chemotherapy,” Dr Tutt said. “The role of olaparib as an adjuvant therapy in any germline BRCA mutation malignancy is untested, and OlympiA sought to examine this in high-recurrence-risk early breast cancer,” he added.
The phase 3 OlympiA trial included 1836 patients with germline BRCA1 or BRCA2 mutations and high-risk early breast cancer without HER2 overexpression. The patients received standard multimodal therapy (including neoadjuvant or adjuvant chemotherapy plus surgery, with or without radiation therapy). Patients were randomized to either olaparib 300 mg twice daily or placebo for 1 year.
Most patients (75.8%) in the olaparib group had a mastectomy, as well as 73.6% of the patients in the placebo group, which was consistent with the genetic makeup of the patients, Dr Tutt said. Approximately 18% of patients had estrogen receptor (ER)-positive breast cancer, and about 82% had triple-negative breast cancer. Approximately 90% of patients with ER-positive breast cancer received endocrine therapy.
The estimated 3-year survival without metastatic disease was 87.5% in the olaparib group and 80.4% in the placebo group. At a median follow-up of 2.5 years, the median overall survival was 3.7% in favor of olaparib compared with the placebo group, but this difference was not statistically significant.
As expected, nausea occurred more frequently in the olaparib arm (57%) compared with the placebo arm (23%), as did fatigue (40% vs 27%), most of which were grade 1 or 2 events. Serious (grade 3 or 4) adverse events were few and consisted of mainly anemia and neutropenia.
“I believe these results are practice changing,” commented Nadine M. Tung, MD, Director of Cancer Risk and Prevention Program and Breast Medical Oncology, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA. “The results of OlympiA reinforce the need to identify germline BRCA carriers among those with early-stage breast cancer,” she said.