At the 2022 San Antonio Breast Cancer Symposium, Mariana Chavez-MacGregor, MD, MD Anderson Cancer Center, Houston, Texas, shared results and insights from the randomized, placebo-controlled phase 3, SWOG S1207 trial evaluating the addition of everolimus to endocrine therapy for patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2−) breast cancer previously treated with chemotherapy.

While the study did not reach its primary end point of improved invasive disease-free survival, Dr Chavez-MacGregor noted the exploratory analysis found premenopausal patients did experience an improvement of invasive disease-free survival and overall survival with everolimus. She also stressed the importance of symptom management when treated patients with these drugs.

Transcript:

My name is Mariana Chavez-MacGregor and I'm an associate professor at the Breast Medical Oncology and Health Services Research Department at the University of Texas MD Anderson Cancer Center. Here at the 2022 San Antonio Breast Cancer Symposium, I had the opportunity to present the results of SWOG 1207. This trial is a randomized, phase 3, placebo-controlled trial, evaluating the role of everolimus, 1 year, in combination with adjuvant endocrine therapy for the treatment of patients with hormone receptor-positive, HER2-negative, early stage breast cancer. This trial enrolled about 900 high-risk patients with early stage breast cancer. All patients were previously treated with neoadjuvant and adjuvant chemotherapy and they were randomized to receive either 1 year of everolimus, with a dose of 10 mg daily, or matched placebo. And all patients received adjuvant endocrine therapy that was the choice of the training physician.

The rationale for this study was to really try to see if we could improve outcomes based on the known data of everolimus being associated with reversion of resistance to endocrine therapy. Primary end point of the study was invasive disease-free survival. The study is a negative study. We did not find any improvement in invasive disease-free survival associated with the addition of everolimus. We also looked at other important secondary end points including overall survival, and we did not see any differences. However, when we look at the exploratory subgroup analysis, we did see that among the 571 premenopausal patients, there was a statistically significant improvement in invasive disease-free survival and overall survival amongst patients treated with everolimus. This is thought-provoking. This is very interesting. This is hypothesis-generating, and I think we're going to try to explore further on this line to really try to understand why.

Some of the other relevant things about this study is that the trial was associated with a very high discontinuation rate. The discontinuation rate amongst patients in the everolimus arm was about 52% compared to only 27% in patients in the placebo arm, really highlighting the importance of symptom management with some of these new drugs. While the study was associated with high discontinuation rate and a high rate of adverse events that were treatment-related in the everolimus arm, we believe that the findings are important. It's important to know that this drug is not going to move forward, at least in this specific setting, but also we think that the observation about premenopausal patients, it's extremely interesting. There might be a difference in biology and while maybe everolimus is not going to be the drug to further evaluate, other inhibitors of this pathway I think are going to need to pay attention to these results, really consider evaluation of these type of drugs in younger patients.

We're real excited to have had the opportunity to present this study and we're excited for all the other presentations during the meeting.

Source:

Chavez-MacGregor M, Miao J, Pusztai L, et al. “GS1-07: Results from a phase III randomized, placebo-controlled clinical trial evaluating adjuvant endocrine therapy +/- 1 year of everolimus in patients with high-risk hormone receptor-positive, HER2-negative breast cancer: SWOG S1207.” Presented at: San Antonio Breast Cancer Symposium; December 5-10, 2022; San Antonio, Texas. Abstract: GS1-07