Dr. Adams on the Utility of Combination CTLA-4 and PD-1 Blockade in Breast Cancer

Sylvia Adams, MD, professor in the Department of Medicine at NYU Grossman School of Medicine and director of the Breast Cancer Center of NYU Langone’s Perlmutter Cancer Center, discusses the utility of combining anti–CTLA-4 and anti–PD-1 agents in breast cancer. 

CTLA-4 inhibitors can elicit a T-cell immune response that is further stimulated by PD-1/PD-L1 inhibitors, explains Adams. 

PD-L1 inhibitors have demonstrated utility when combined with chemotherapy in the breast cancer setting, says Adams. For example, in March 2019, atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) was granted accelerated approval by the FDA for the treatment of patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer. 

Conversely, CTLA-4 inhibitors have not elicited the same benefit in breast cancer and it is known that these agents are associated with significant toxicity, explains Adams. As such, these agents are typically reserved for use in the clinical trial setting, for patients who have not responded to standard therapies and have a poor prognosis. 

Notably, the combination of CTLA-4 and PD-1 blockade has demonstrated success in melanoma and lung cancer. Based on this promise, this approach has recently been evaluated in a rare breast cancer subtype called metaplastic breast cancer. Results from the phase 2 DART trial showed early clinical activity with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) in this patient population, concludes Adams.