NCCN: Updated Guidelines Reflect Advances, ‘Immunotherapy Era’ for Breast Cancer

Updates to the National Comprehensive Cancer Network (NCCN) Guidelines^® on breast cancer reflect maturing evidence bases and expanding treatment options, including a recently approved immunotherapy regimen for some patients with locally advanced or metastatic disease, according to speakers at the 2019 NCCN Annual Conference, held March 21–23 in Orlando, Florida.

“There are many new and emerging options for ER [estrogen receptor]-positive breast cancer,” noted William J. Gradishar, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. “Carefully selecting patients for specific therapies-and understanding the mechanisms of resistance-remain challenges.”

Treating early-stage, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer involves selection of an optimal systemic therapy and individualized surgical management of the axilla, said Melinda L. Telli, MD, of the Stanford Cancer Institute.

“The natural history of breast cancer is long,” Telli noted. “There is an ongoing risk of breast cancer distant recurrence and breast cancer death, even 15 or 20 years after diagnosis.”

For premenopausal women, adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor for 5 years is recommended. Available evidence suggests that among premenopausal women with HR-positive early breast cancer, adjuvant exemestane plus ovarian suppression significantly reduces recurrence compared with tamoxifen plus ovarian suppression. (Five-year disease-free survival [DFS5] was 91% vs 87%.)

Recent treatment advances for advanced breast cancers are also reflected in the newly updated NCCN Guidelines^® for invasive breast cancer (Version 1.2019), which now include recommendations for poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib or talazoparib) in addition to platinum-based chemotherapy (carboplatin or cisplatin) for patients with HER2-negative tumors and germline BRCA1/2 mutations-and a new immunotherapy regimen for patients with advanced programmed death ligand 1 (PD-L1)-positive triple negative breast cancer.

The US Food and Drug Administration (FDA) announced accelerated approval of atezolizumab (an engineered monoclonal antibody targeting PD-L1) plus nab-paclitaxel for patients with inoperable, PD-L1–positive locally advanced or metastatic triple negative breast cancer, following publication of findings from the phase III IMpassion130 trial in November (ClinicalTrials.gov identifier: NCT02425891). It was the first FDA-approved immunotherapy regimen for breast cancer. (Among patients with PD-L1–positive tumors, median progression-free survival was 7.5 months among patients receiving the combination regimen vs 5.0 months among those receiving placebo plus nab-paclitaxel; hazard ratio [HR], 0.62; 95% CI, 0.49–0.78; P < .001.)

“As of a week ago, we have an approved immunotherapy for breast cancer,” Gradishar said. “The era of immunotherapy for breast cancer has arrived.”

The promise of immunotherapy against breast cancer has been discounted by many because ER-positive tumors were not believed to be immunologically “hot,” Gradishar said. “If we look at immunogenicity by tumor types, breast cancer falls in the middle.”

Immune checkpoint inhibitor monotherapy offers only modest response rates in breast cancer (as low as 2.8% for avelumab among women with ER+/HER2-negative breast cancer and 8.6% objective response rate for avelumab and 10% for atezolizumab among patients with triple negative breast cancer, for example), Gradishar cautioned.

Response rates are particularly low in later lines of treatment, Gradishar said. “If used in later lines, the probability of benefit is quite low,” he said.

For advanced HER2-positive breast cancers, pertuzumab, trastuzumab, and docetaxel remains the preferred regimen.

Dr. Telli disclosed scientific advisor positions with Aduro, Celgene, Genentech, Immunomedics, Merck & Co., and Pfizer.