Long-Term Survival Benefit With Olaparib in Mets Breast Cancer?

The PARP inhibitor olaparib (Lynparza) may confer a long-term survival benefit in women with HER2-negative metastatic breast cancer and a germline BRCA mutation, most notably in the first-line setting, according to the latest results from the phase 3 OlympiAD trial.

Although the median overall survival benefit for the overall population was just over 2 months after more than 2 years of follow-up among women who received olaparib vs physician’s choice of chemotherapy, the median overall survival benefit was nearly 8 months among patients who received olaparib in the first-line setting (22.6 vs 14.7 months).

This post hoc exploratory analysis supports the possibility of a long-term survival benefit with olaparib, particularly when used first-line for metastatic breast cancer, first author Mark E. Robson, MD, Memorial Sloan Kettering Cancer Center, New York City, and colleagues noted.

The findings were published online last month in the European Journal of Cancer.

Initial outcomes from the OlympiAD trial, which compared olaparib with physician’s choice of chemotherapy in patients who had received up to two prior lines of chemotherapy for metastatic disease, were published in 2017 and showed a statistically significant 2.8-month progression-free survival (PFS) benefit with olaparib (7.0 vs 4.2 months), at a median of 14 months follow-up, as reported by Medscape Medical News. At that time, however, there was no mature overall survival data.

The new analysis includes an additional 25.7 months of follow-up during which overall survival was assessed every 6 months. All OlympiAD participants had received an anthracycline unless contraindicated, a taxane in the neoadjuvant, adjuvant, or metastatic setting, and no more than two chemotherapy regimens for metastatic breast cancer. Patients were randomly assigned to receive 300 mg olaparib tablets twice daily or predeclared single-agent physician’s choice of capecitabine, vinorelbine, or eribulin until objective disease progression or unacceptable toxicity.

In the overall population of 302 patients, 38 (12.6%) remained in the study — 10 of whom continued to receive olaparib and 28 of whom had stopped treatment. The main reason for study termination among the remaining patients was death (n = 232).

The authors found that median overall survival was statistically similar at 19.3 months for olaparib and 17.1 for chemotherapy (hazard ratio [HR], 0.89), and 3-year overall survival was 27.9% and 21.2%, respectively.

However, in the subgroup of patients receiving olaparib or chemotherapy as first-line treatment, median overall survival was 22.6 vs 14.7 months (HR, 0.55; 95% CI, 0.33 – 0.95). In this group, 40.8% of patients in the olaparib arm were alive at 3 years vs 12.8% in the chemotherapy group.

The investigators reported no new serious adverse events related to olaparib but did note several caveats related to the study findings, including the similar progression-free survival in both treatment arms across subgroups.

Overall, the numeric overall survival benefit between olaparib and physician’s choice of chemotherapy revealed “the possibility of greatest long-term benefit among patients who had not received prior chemotherapy for metastatic disease,” the authors conclude. But “these exploratory findings should be investigated further,” they add.

This study was supported by AstraZeneca and Merck Sharp & Dohme LLC. Robson reported honoraria, research grants, personal fees, and/or other support from Intellisphere, MH, Physicians’ Education Resources, Research to Practice, AZ, Merck, Pfizer, Change Health Care, Epic Sciences, and Zenith Epigenetics. He also reported funding from an NIH/NIC Cancer Center Support Grant and the Breast Cancer Research Foundation. Several other co-authors reported relationships with industry. The full list can be found with the original article.

Euro J Cancer. Published online February 14, 2023. Abstract

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at  [email protected] or on Twitter: @SW_MedReporter.

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