Lee S. Schwartzberg, MD, FACP
Recent advancements in the field of breast cancer are reshaping the treatment paradigm for subsets of patients with the disease, bringing new therapies and strategies into focus, according to experts who participated in an OncLive Peer Exchange®
The panelists said research from key abstracts presented during the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5-9 in Texas, generated fresh insights into the treatment of pre- and perimenopausal women with hormone receptor (HR)-positive disease, emerging antibody–drug conjugates for HER2-positive and triple-negative breast cancer (TNBC), and the potential for immunotherapy. The experts were particularly enthusiastic about the continuing exploration of CDK4/6 inhibitors, a class of drugs that has emerged since 2015 for women with HR-positive, HER2-negative breast cancer. They also noted the expansion of PARP inhibitors from ovarian to breast cancer. In January 2018, the FDA approved olaparib (Lynparza), a PARP inhibitor, for patients with metastatic HER2-negative disease and a germline BRCA
mutation after prior treatment with chemotherapy.
“I think the science in breast cancer is really making tangible differences in our patients’ lives now and that’s exciting,” said Lee S. Schwartzberg, MD.
Hormone-Driven Breast Cancer
Three CDK4/6 inhibitors are now approved for patients with metastatic, HR-positive, HER2- negative breast cancer. Palbociclib (Ibrance) was the first agent approved in this drug class in 2015, followed by abemaciclib (Verzenio) and ribociclib (Kisqali) in 2017. These therapies have been targeted for postmenopausal women.
Research at SABCS is likely to expand that population. “We now have another option that is formally clinically tested for premenopausal women—to use ovarian suppression and an aromatase inhibitor [AI],” said Schwartzberg.
According to the phase III MONALEESA-7 trial, adding ribociclib to first-line endocrine therapy (tamoxifen/nonsteroidal AI with goserelin) significantly prolongs progression-free survival (PFS) in both pre- and perimenopausal women with HR-positive, HER2-negative advanced breast cancer.1
That’s significant because “a lot of times, people think you have to take the ovaries out of these patients,” said Hope S. Rugo, MD. “Now we know we don’t have to take the ovaries out.”
Adding ovarian suppression to tamoxifen therapy improves outcomes in premenopausal women with HR-positive, HER2-negative breast cancer; the combination of an AI plus ovarian suppression may be even more beneficial, according to updated data from the TEXT and SOFT trials. “One thing that was really striking to me was that women who were under the age of 35 had this enormous benefit,” Rugo said. “There was more than a 15% difference in disease-free survival (DFS) in patients who got aromatase inhibitor plus ovarian suppression versus tamoxifen, and then an 11.5% benefit in patients who got tamoxifen plus ovarian suppression. What that means is you can give patients either option.”
However, toxicities seem to be more common in patients treated with AIs, and that’s an important factor to consider. “We’re already making women miserable enough with luteinizing hormone– releasing hormone suppression. We make them more miserable with an AI on top of it,” said session moderator Adam M. Brufsky, MD, PhD.
CDK4/6 inhibition plus an AI has also been shown to improve PFS and quality of life in postmenopausal women with HR-positive, HER2-negative advanced breast cancer.2 That’s “very important in the metastatic and palliative setting,” said Komal Jhaveri, MD, noting that available data also suggest significant reductions in pain scores by 8 weeks. The fact that CDK4/6 inhibition doesn’t seem to disrupt quality of life means it may also be a good option for asymptomatic patients with metastases.