Olaparib Improves Overall Survival in HER2- Early Breast Cancer

Charles E. Geyer, MD, co-director of University of Pittsburgh Medical Center’s Hillman Cancer Center’s National Cancer Institute National Clinical Trials Network efforts, and chief scientific officer of the National Surgical Adjuvant Breast and Bowel Project, discusses the efficacy of olaparib (Lynparza) in the OlympiA study (NCT02032823) of patients with BRCA-positive, HER2-negative high-risk early breast cancer.

The OlympiA trial randomized patients who had previously received definitive local treatment and adjuvant or neoadjuvant chemotherapy to receive olaparib or placebo for up to 12 months. According to Geyer, the key primary end point was invasive disease-free survival (IDFS) at 3 years, and results at a median follow-up of 2.5 years showed that 23% in the control arm had disease recurrence or died, for an IDFS rate of 77% with placebo versus 86% for those who received olaparib.

Since distant metastases are a major factor for mortality in breast cancer, investigators also explored distant disease-free survival (DDFS) and found that it was 87.5% for those who received olaparib versus 80.4% for those who did not.

Updated results at 3.5 years of follow-up found the trial had reached a statistically significant improvement in overall survival translating to a 32% reduction in risk of death (stratified hazard ratio, 0.68; 95% CI, 0.50-0.91; P = .0091). According to Geyer, this difference will increase over time to align with the difference in DDFS, as patients who develop distant disease have poor long-term survival. Patients will be assessed annually for 10 years after randomization plus 10 years of follow-up to evaluate long-term survival outcomes.

TRANSCRIPTION:

0:08 | [In our patient population, we thought], let's look at patients who had standard therapy; [they] still have IDFS rates at 3 years of less than 80%. We saw that in our control group, so we were successful there. Happily, in the patients who had received the olaparib, that 77% increased up to 86%, an absolute 9 [percentage point] improvement, so [it was] a very gratifying step up for staying alive and cancer-free.

0:40 | We also did the study to specifically then look at and really focus on the most feared part of breast cancer, and that is cancer that comes back out in the body: distant metastasis, because that's what will take a patient's life. And we saw virtually the same sort of improvement. The percentage of patients who were alive and free of distant metastases was 81%, it went up to 88%. So again, very meaningful improvement. Now, at that early point, our survival question—just looking at how many patients are still alive—we saw that patients getting olaparib seem to be doing better. But it was early enough in the study that we needed more follow-up to really be sure if that apparent reduction in deaths was statistically valid.

1:35 | What we reported on recently, in the European Society of Medical Oncology Plenary, what the FDA basically included in their approval, was that yes, survival is also improved by about an absolute 3.5 [percentage points]. We expected that probably will get larger over times, because we know when patients develop distant disease, unfortunately, our therapies aren't able to cure it. So though that 7 [percentage point] difference [in DDFS] there…probably will lead to [OS] improvement, but we already are seeing a meaningful improvement with the olaparib. So, the efficacy side of the drug is really quite strong at an early point in the trial analysis.