Dr. Tolaney Highlights New Breast Cancer Combination Therapies

Sara Tolaney, MD, MPH, associate director, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, discussed new combination treatments for patients with breast cancer at the 2019 ASCO Annual Meeting.

The MONALEESA-7 study, a phase III trial, evaluated the responses of premenopausal patients with hormone receptor—positive/HER2-negative advanced breast cancer to receiving ribociclib (Kisqali), a CDK4/6 inhibitor, with endocrine therapy. Overall survival (OS), evaluated after 173 deaths, was greater in patients treated with ribociclib and endocrine therapy rather than placebo and endocrine therapy; the median OS was not reached versus 40.9 months, respectively. Estimated OS rates at 42 months for ribociclib/endocrine therapy versus placebo/endocrine therapy were 70.2% versus 46%, respectively. Ribociclib paired with endocrine therapy saw a 29% decline in deaths compared with placebo and endocrine therapy, Tolaney said.

The SOPHIA study, a randomized phase III trial, compared margetuximab versus trastuzumab (Herceptin), each combined with chemotherapy, in patients with HER2-positive metastatic breast cancer after prior anti-HER2 therapies. Researchers found margetuximab prolonged progression-free survival (PFS) over trastuzumab at a median 5.8 versus 4.9 months, respectively. In 524 patients with baseline measurable disease, margetuximab had a better overall response rate (ORR) at 22% compared with trastuzumab at 16%. The effects of treatment were more pronounced in patients with CD16A genotypes containing a 158F allele. Although the outcomes were similar, margetuximab may offer benefits over trastuzumab, especially for patients who have CD16A genotypes.

The randomized, phase III NALA trial compared the combinations of neratinib (Nerlynx) and capecitabine (Xeloda) versus lapatinib (Tykerb) and capecitabine in patients with HER2-positive breast cancer previously treated by ≥2 HER2-directed regimens. Of the 621 patients, the risk of disease progression was reduced by 24% with neratinib rather than lapatinib. Additionally, in neratinib versus lapatinib, 6- and 12-month PFS rates were 47.2% versus 37.8% and 28.8% versus 14.8%. OS rates for neratinib versus lapatinib at 6- and 12-months were 90.2% versus 87.5% and 72.5% versus 66.7%. An extremely interesting aspect, according to Tolaney, was the time to intervention for symptomatic central nervous system disease (overall cumulative incidence 22.8% vs 29.2%) was delayed with neratinib versus lapatinib. Researchers found that neratinib combined with capecitabine greatly improved PFS and seemed to improve OS versus lapatinib and capecitabine. Tolaney said it will be a challenge to integrate the neratinib and capecitabine into practice because “there are now so many HER2 therapies in this [third-line] setting.”

Tolaney is hopeful for the future of breast cancer and said, “There are so many new and exciting drugs that continue to come around. We’re all very hopeful that will continue to improve outcomes for our patients.”