Adjuvant olaparib (Lynparza) significantly improves overall survival (OS), compared with placebo, for patients with high-risk, early-stage, HER2-negative, germline BRCA-mutated breast cancer, according to the latest results from the pivotal phase 3 OlympiA trial.
Olaparib was recently approved for this indication, as reported by Medscape Medical News; the approval was based on earlier results from this same trial.
The new results come from a second prespecified event-driven analysis of OS.
At a median follow-up of 3.5 years, OS was 89.8% with olaparrib, vs 86.4% with placebo (hazard ratio [HR], 0.68), first author Andrew Tutt, MD, reported at the European Society of Medical Oncology March virtual plenary meeting.
This equates to a 32% reduction in the risk of death with olaparib, said Tutt, director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research and a professor of clinical oncology at King’s College London.
“These findings are clearly critically important and I think will define practice for this subset of patients,” said invited discussant Mark E. Robson, MD.
Important clinical questions remain, including the question regarding the best course of treatment for patients with triple-negative disease who did not achieve a pathologic clinical response after neoadjuvant chemotherapy and for patients with ER-positive disease, said Robson, chief of the Breast Medicine Service in the Department of Medicine at Memorial Hospital and a member of the Memorial Sloan Kettering Cancer Center, New York.
Still, the findings are “clearly practice changing,” he said.
“In my opinion, olaparib should be offered to anyone who meets entry criteria for this study,” he added.
First Trial of PARP Inhibitor as Adjuvant Therapy
The recent approval of the new indication for oalapraib was based on previously published findings from OlympiA, the first phase 3 randomized clinical trial to test a PARP inhibitor as adjuvant therapy.
OlympiA results were presented during the plenary session of the American Society of Clinical Oncology (ASCO) 2021 annual meeting and were published in The New England Journal of Medicine, as reported at the time by Medscape Medical News.
At the first event-driven interim analysis, the data cutoff of which was in March 2020, olaparib significantly improved invasive disease–free survival (IDFS) and distant disease–free survival (DDFS), compared with placebo, but OS did not cross the prespecified boundary for significance (P < .01), Tutt explained.
For the second interim analysis, the data cutoff was in July 2021 and was planned after 330 IDFS events.
“The difference in the OS rate at 3 years is 3.8%, and it’s 3.4% at 4 years,” Tutt said. “The olaparib treatment effect was consistent, without evidence of significant heterogeneity across major subgroups, including the BRCA1, BRCA2, hormone receptor–positive, and triple-negative breast cancer groups.”
IDFS, the primary study endpoint, was consistent with previous estimates that showed a benefit with olaparib vs placebo (HR, 0.63), with an 8.8% difference between the groups at 3 years and a 7.3% difference at 4 years.
The secondary study endpoint of DDFS was also consistent with previous estimates showing a benefit (HR, 0.61), with a difference of 7% at 3 years and 7.4% at 4 years, he said.
No excess adverse events, including serious adverse events, were observed, and no additional adverse events leading to death have been reported since the first interim analysis, he noted.
OlympiA was funded by AstraZeneca and Merck and Co, Inc. Tutt reported numerous relationships with industry. Robson reports uncompensated relationships with a number of companies that make PARP inhibitors and research funding and/or editorial support from AstraZeneca, Merck, and Pfizer.
ESMO March Virtual Plenary: Abstract VPI-2022. Presented March 16, 2022.
Sharon Worcester is an award-winning medical journalist at MDedge News, part of the Medscape Professional Network.