Mariana Chavez Mac Gregor, MD, MSC, associate professor, Department of Health Services Research, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, discusses key efficacy and safety data from the phase 3 SWOG S1207 trial (NCT01674140) of everolimus (Afinitor) in hormone receptor (HR)–positive, HER2-negative breast cancer. 

This randomized, placebo-controlled trial investigated the role of the addition of the mTOR-inhibitor everolimus plus standard adjuvant endocrine therapy in high-risk patients, Chavez Mac Gregor begins. Patients were randomly assigned 1:1 to either the investigator’s choice of adjuvant endocrine therapy plus 1 year of everolimus or placebo. The trial’s primary end point was invasive disease-free survival (IDFS), with secondary end points including overall survival (OS) and safety. Subset analyses included a preplanned evaluation according to risk group and exploratory analyses of menopausal status and age.

Final analysis by risk group revealed that everolimus elicited no improvement in survival outcomes among postmenopausal patients, Chavez Mac Gregor states. However, an exploratory analysis of 581 premenopausal patients did show a statistically significant increase in both IDFS and OS, Chavez Mac Gregor says. Despite the negative outcome of this study, these data were thought-provoking and hypothesis-generating, she emphasizes.

Safety data showed that patients treated with everolimus also experienced a higher rate of grade 3 and 4 adverse events (AEs) compared with patients in the control group, Chavez Mac Gregor continues. Moreover, the treatment discontinuation rate was higher in the experimental arm due to treatment-related adverse events, she states. These results signify the need for improved understanding of the drug’s toxicity profile, tolerability, and AE management in this patient population, Chavez Mac Gregor explains. Future research should aim to address the low completion rate and high toxicity associated with everolimus.

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Mariana Chavez Mac Gregor, MD, MSC, discusses key efficacy and safety data from the phase 3 SWOG S1207 trial of everolimus in hormone receptor–positive, HER2-negative breast cancer.
 

Dr. Chavez Mac Gregor on Key Results From SWOG S1207 in HR+/HER2- Breast Cancer

Mariana Chavez Mac Gregor, MD, MSc, associate professor, Department of Health Services Research, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, discusses the use of chemotherapy in patients with node-positive, hormone receptor (HR)-positive, HER2-negative breast cancer.

Patients with HR-positive tumors should receive endocrine therapy, but whether or not all patients with node-positive tumors need to receive chemotherapy remains unclear. Many clinical trials are evaluating this, says Chavez Mac Gregor—specifically, the highly anticipated RxPONDER trial. These trials will shed more light on whether or not patients with 1 to 3 positive lymph nodes with recurrence scores less than 25 benefit from chemotherapy or not.

Retrospective data do suggest that the biology is very important, she adds. Even in this group of higher-risk patients, those with lower recurrence scores may not benefit from chemotherapy.

For example, data from the MINDACT trial, in which the genomic assay MammaPrint was used, showed that patients who are high-risk clinically but low-risk genomically have excellent outcomes. Despite this, many patients with lymph node involvement continue to receive chemotherapy, says Chavez Mac Gregor. However, providers are beginning to learn how to tailor and personalize treatment based not only on the extent of disease, but also its biology.

Mariana Chavez Mac Gregor, MD, MSc

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Dr. Chavez Mac Gregor on Key Results From SWOG S1207 in HR+/HER2- Breast Cancer

Dr. Chavez Mac Gregor on Chemotherapy in Node-Positive HR+/HER2- Breast Cancer