Charles E. Geyer, Jr, MD

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 end point that was met within the OlympiA study (NCT02032823).

The randomized, double-blind, placebo-controlled, multicenter, phase 3 trial, aimed to evaluate the efficacy and safety of olaparib (Lynparza) in patients with germline 

1/2 mutations and high-risk HER2 negative primary breast cancer who had completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.

The study met its primary end point of meaningful and statistically improved invasive disease-free survival at the time of its initial interim efficacy analysis. Findings of the 

 were further presented during the March 2022 ESMO Virtual Plenary.

The primary end point for OlympiA was presented at the our annual ASCO meeting in 2021 almost a year ago. That was when we conducted the initial interim efficacy analysis. What we saw at that point was that olaparib relative to placebo was already showing a meaningful and statistically improvement in our end point, called invasive disease-free survival. Invasive disease-free survival is actually a composite endpoint that is describing a group of women who are alive and free of any breast cancer or any other type of cancer. It's kind of a composite end point, but it's an important one, because it helps us get a sense of both efficacy and safety.

 What we saw at that point, with about 2 and a half years of median follow up, [is that] the group of women who had had standard therapy, but then received placebo, 23% of them had already had a recurrence or had died. That's kind of what we were targeting in our patient population. We thought, let's look at patients who is standard therapy, still have invasive disease-free survival 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% improvement, a very gratifying step up for staying alive and cancer free. We also did the study to specifically then look at and 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%. Again, very meaningful improvement.

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Charles Geyer, MD, discusses the end point that was met within the OlympiA study.


Invasive Disease-Free Survival as an End Point for the OlympiA Trial 

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 

-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; 

 = .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.

 [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.

 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.

 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.

Charles E. Geyer, MD, discusses the efficacy of olaparib in the OlympiA study of patients with BRCA-positive, HER2-negative high-risk early breast cancer. 

Olaparib Improves Overall Survival in HER2- Early Breast Cancer

Charles E. Geyer, Jr, MD, professor of medicine at Virginia Commonwealth University School of Medicine, associate director for clinical research and Harrigan, Haw, Luck Families Chair in Cancer Research at Massey Cancer Center, discusses the impact of pertuzumab (Perjeta) in the treatment of patients with HER2-positive breast cancer at the 2018 San Antonio Breast Cancer Symposium.

Pertuzumab is a very important drug in the early treatment of patients with HER2-positive breast cancer, explains Geyer. In large part, its efficacy was demonstrated in results of the CLEOPATRA trial in metastatic disease. These antibodies were developed with an intent to engage the immune system, and they had yet to demonstrate that intent until CLEOPATRA, says Geyer.

Charles E. Geyer, Jr, MD | Authors

Articles

Invasive Disease-Free Survival as an End Point for the OlympiA Trial

Olaparib Improves Overall Survival in HER2- Early Breast Cancer

Impact of Pertuzumab in HER2-Positive Breast Cancer