Olaparib Improves Survival in BRCA+, High-Risk Early Breast Cancer

The PARP inhibitor demonstrated impressive overall survival benefit in patients with BRCA-mutated, HER2-negative, high-risk early breast cancer.

Adjuvant olaparib (Lynparza) induced a significant improvement in overall survival (OS) among previously treated patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer, according to findings of the OlympiA trial (NCT02032823) that were recently presented at the March 2022 ESMO Virtual Plenary.

In the analysis, investigators determined that olaparib reduced the risk of death by 32% compared with placebo (HR, 0.68; 98.5% CI, 0.47-0.97; P = .009). Furthermore, the 3-year survival rate was 92.8% with the PARP inhibitor (95% CI, 90.8%-94.4%) compared with 89.1% for those on placebo (95% CI, 86.7%-91.0%). At a 4-year follow-up, the survival rate was 89.8% (95% CI, 87.2%-91.9%) vs. 86.4% (95% CI, 83.6%-88.7%), respectively.

Notably, these analyses are based on Kaplan-Meier estimates and are descriptive only.

“We knew that even with our best standard chemotherapy, surgery, [or] radiation therapy, [this high-risk population] would still be left with more than a 20% chance of their cancer coming back within the next 3 to 5 years [following treatment],” said Charles E. Geyer, MD, FACP, chief scientific officer of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, in an interview with Oncology Nursing News®. “We had an unmet need there. [Therefore], we've been looking for possible new therapeutics to try to improve the outcomes.”

Geyer noted that PARP inhibitors have now been under investigation for more than a decade as a specific targeted therapy designed for patients whose disease expresses these mutations. Although there have been many studies assessing the agent among patients with metastatic disease or advanced ovarian cancer, the OlympiA trial was unique because it looked at olaparib in the curative breast cancer population.

“We now are seeing statistically improved, significant improvement in survival [in our study population]. Right now, [there is] already a 3.5% improvement in survival,” he said. “[The] very good, consistent efficacy data, at a relatively early point in the study, is really demonstrating the efficacy of the drug.”

Olaparib was recently approved by the FDA an adjuvant treatment for patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer and who have already undergone chemotherapy before or after surgery. The regulatory decision was primarily supported by findings from the OlympiA trial.

The phase 3, double-blind, parallel group, placebo-controlled, international OlympiA trial was designed to evaluate the efficacy and safety of olaparib against placebo as an adjuvant treatment for patient who have already completed definitive local treatment and neoadjuvant or adjuvant chemotherapy for BRCA-mutated, HER2-negative high-risk early breast cancer. The trial’s primary objective was to evaluate invasive DFS (iDFS), defined as time form randomization to first locoregional or distant recurrence or new cancer or a new cancer or death from any cause. OS represented the key secondary measure.

Previous findings from the OlympiA trial found that the agent yielded statistically significant improvements in iDFS; patients receiving olaparib had reduced their risk of invasive breast cancer recurrences, secondary cancers, or death by 42% (HR, 0.58; 99.5% CI, 0.41-0.82; P < .0001).

Throughout the trial, olaparib demonstrated a safety and tolerability profile that was consistent with previous assessments. The most common adverse events (AEs) included nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Ten percent of patients needed to discontinue treatment due to an adverse event. The most common serious AEs were anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue (1.8%).

“So far, it's been very gratifying to see no difference between placebo and the olaparib in this patient population, but this remains an important part of the study,” Geyer concluded. “We are going to follow these patients out [for another] 10 years. We are going to be getting more and more information about how well the drug works and any possible late effects.”

However, currently, Geyer noted, the efficacy and tolerability data indicate that this drug is worthy of consideration as a treatment option for this patient population.

Reference

  1. Lynparza (olaparib) reduced risk of death by 32% in patients with germline BRCA–mutated, HER2–negative high–risk early breast cancer in phase 3 OlympiA trial. Merck. News release. March 16, 2022. Accessed March 22, 2022. https://bit.ly/36ByYeb
  2. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. AstraZeneca. News release. March 11, 2022. Accessed March 11, 2022. https://bit.ly/3tQePcn