Olaparib in Breast Cancer: PFS Is Significant but OS Is Not

Alexander M. Castellino, PhD

April 18, 2018

CHICAGO — A few months ago, olaparib (Lynparza, AstraZeneca) was the first drug approved to treat women with advanced breast cancer with germline mutations in BRCA.

That approval was based on a significant improvement in progression-free survival (PFS) compared with standard chemotherapy shown in the OlympiAD trial. The results led to quite some excitement among breast cancer researchers, as for example in the Medscape Oncology commentary "OlympiAD: Olaparib Captures Gold for BRCA-Mutated Breast Cancer Patients."

Now, however, a final analysis of OlympiAD results shows that overall survival (OS) did not significantly improve.

The difference in survival between the two groups was 2.2 months longer for olaparib (median OS, 19.3 months with olaparib vs 17.1 months with standard chemotherapy).

The new OS data were presented here at the American Association for Cancer Research (AACR) 2018 Annual Meeting.

Mark E. Robson, MD, medical oncologist and chief of the breast medicine service at the Memorial Sloan Kettering Cancer Center, New York City, presented the details.

At the final analysis, of 302 patients randomly assigned, 205 received olaparib and 91 received chemotherapy (investigator's choice of capecitabine [Xeloda, Hoffmann-La Roche]), eribulin [Halaven, Eisai], or vinorelbine [Navelbine, Pierre Fabre]).

With a hazard ratio (HR) of 0.90, patients receiving olaparib had a 10% reduced risk for death compared with those receiving chemotherapy, but these data did not reach statistical significance.

However, more patients in the chemotherapy group received subsequent therapy (with poly [adenosine diphosphate-ribose] polymerase inhibitors, chemotherapy, platinum, and hormonal treatment).

With 64% maturity at final OS data cutoff, approximately 13% of patients continued receiving olaparib and no patients continued chemotherapy.

Benefit with olaparib was greatest for patients who received olaparib as first-line therapy: 22.6 months with olaparib vs 14.7 months with chemotherapy (HR, 0.51; 95% confidence intervals, 0.29 - 0.90; P = .02). OS was not significant for patients who received olaparib as a later line of therapy (median OS, 18.8 months vs 17.2 months for chemotherapy).

For all other stratification groups (prior platinum therapy, receptor status, triple-negative breast cancer), OS was not significant for olaparib vs chemotherapy.

Robson also noted that longer-term exposure to olaparib did not show any relevant cumulative toxicity with the drug. "Olaparib safety profile was consistent with the primary analysis," Robson noted.

In the extended safety analysis, grade 3 or 4 adverse events were reported for 38% of patients receiving olaparib and 50% of patients receiving standard chemotherapy.  Nineteen percent of patients received olaparib for more than 18 months and 7% did so for more than 24 months.

Robson pointed out that OlympiAD was not powered to show an OS difference between olaparib and standard chemotherapy.

Another trial now underway is powered to show such an effect. A phase 3 study in approximately 1800 patients, called OlympiA, is evaluating olaparib as adjuvant treatment in patients with germline BRCA–mutated, human epidermal growth factor receptor 2–negative breast cancer, with results expected in 2020.

Unlikely to Affect Use of Olaparib

Approached for comment, Eric P. Winer, MD, told Medscape Medical News that the lack of OS significance is unlikely to affect the use of olaparib in women with advanced breast cancer with germline mutations in BRCA.

Winer is chief of the Breast Oncology Center at the Susan F. Smith Center for Women's Cancers and the Thompson Chair in Breast Cancer Research at Dana-Farber Cancer Institute, Boston, Massachusetts.

"I don't think this will have a substantial effect on patterns of use," Winer told Medscape Medical News. "Olaparib is better tolerated than chemotherapy and results in a significant PFS advantage and a nonsignificant increase in OS," he said. 

"I think the results underscore the fact that we need to continue to search for better therapies in this group of patients," Winer added.

Robson discloses relationships AstraZeneca, McKesson, AbbVie, Myriad Genetics, and Medivation.

American Association for Cancer Research (AACR) 2018 Annual Meeting. Abstract CT038. Presented April 15, 2018.

Follow Medscape Oncology on Twitter: @MedscapeOnc

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