Long-Term Data Show Lynparza Significantly Improves Survival in Germline BRCA Mutated, HER2-Negative Breast Cancer

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Data from the OlympiA Phase III trial (NCT02032823) show that Lynparza (Olaparib; AstraZeneca, Merck) produced a long-term and clinically meaningful improvement in the risk of death, invasive disease-free survival (IDFS), and distant disease-free survival (DDFS) at six years in patients with germline BRCA-mutated (gBRCAm) HER2-negative high-risk early breast cancer.^1,2

These latest data add to primary findings published earlier this year by The New England Journal of Medicine (NEJM), which showed that adjuvant Lynparza administered after the completion of local treatment and neoadjuvant or adjuvant chemotherapy achieved significantly longer survival free of invasive or distant disease compared to placebo, along with a limited impact on quality of life.

“These exciting long-term data from OlympiA confirm that adjuvant treatment with olaparib for one year continues to deliver clinically meaningful survival benefit for patients with germline BRCA-mutated high-risk HER2-negative early breast cancer even after six years, with benefit persisting in all subgroups and with toxicity and pregnancy data reassuring for this generally younger group,” co-principal trial investigator Judy E. Garber, chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute said in a press release. “These data reinforce the importance of germline BRCA testing at the time of diagnosis, so we can identify all eligible patients who may benefit from treatment with olaparib as early as possible.”¹

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as first-line maintenance for BRCAm advanced ovarian cancer; first-line maintenance HRD-positive advanced ovarian cancer in combination with bevacizumab; maintenance BRCA-mutated recurrent ovarian cancer; adjuvant treatment of gBRCAm, HER2-negative, high-risk early breast cancer; gBRCAm, HER2-negative metastatic breast cancer; first-line maintenance gBRCAm metastatic pancreatic cancer; HRR gene-mutated metastatic castration-resistant prostate cancer; BRCAm metastatic castration-resistant prostate cancer in combination with abiraterone and prednisone or prednisolone.

Trial Design

The double-blind, parallel group, placebo-controlled, multicenter OlympiA trial analyzed the efficacy and safety of Lynparza tablets compared to placebo as a 12-month adjuvant treatment for adults with gBRCAm HER2-negative early breast cancer who completed neoadjuvant or adjuvant chemotherapy. In total, 1836 patients were randomly assigned to the Lynparza cohort or placebo cohort.

The trial’s primary endpoint is IDFS, which is defined as time from randomization to date of first loco-regional or distant recurrence, or new cancer or death from any cause. Key secondary endpoints include DDFS and overall survival, defined as time from randomization to documented evidence of first distant recurrence of breast cancer or death without distant recurrence.

Results

At a median follow-up of 6.1 years, among eligible patients who completed local treatment and standard neoadjuvant or adjuvant chemotherapy, Lynparza was found to lower the risk of death by 28% (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56-0.93) compared to placebo. Further, 87.5% of those administered Lynparza remained alive compared to 83.2% of patients given a placebo.¹

Earlier results published by NEJM show found that at a median follow-up of 2.5 years, three-year IDFS was 85.9% among patients administered Lynparza compared to 77.1% among patients given a placebo (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). Three-year DDFS was 87.5% in the Lynparza cohort compared to 80.4% in the placebo cohort (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001).³

“Two years ago, Lynparza became the first and only PARP inhibitor to demonstrate a survival benefit in germline BRCA-mutated, HER2-negative and high-risk early-stage breast cancer,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release. “To see this benefit continue after six years of follow-up is tremendous for patients and reinforces how Lynparza is continuing to transform the treatment of BRCA-mutated early-stage breast cancer.”¹

References

1. Lynparza demonstrated clinically meaningful prolonged survival benefit in early breast cancer in OlympiA Phase III trial. News release. AstraZeneca. December 11, 2024. Accessed December 16, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html#

2. Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer (OlympiA). ClinicalTrials.gov. Updated August 23, 2024. Accessed December 16, 2024. https://clinicaltrials.gov/study/NCT02032823

3. Tutt A., et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021;384:2394-2405. DOI: 10.1056/NEJMoa2105215. Vol. 384 No. 25.