Efficacy of immunotherapy in older patients with triple-negative breast cancer: a systematic review

Immune checkpoint inhibitors (ICI) have emerged as a promising treatment for patients with triple-negative breast cancer (TNBC); however, there exists a notable gap in our understanding of their efficacy within the older patient population. The objective of this systematic review is to evaluate the efficacy of ICI in patients with TNBC who are 65 and older. We conducted a comprehensive systematic search using Medline, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform of randomized controlled trials (RCTs) reporting efficacy of ICI from January 2013 to September 2023. Our systematic review identified 18 full-text papers encompassing 11 unique RCTs. Only four RCTs presented results for patients 65 and older: KEYNOTE 355, KEYNOTE 522, IMPASSION 130, and IMPASSION 131. In these four studies, 602 patients out of 3215 patients (18.7%) were 65 and older. The overall risk of bias was rated low or intermediate in all 11 RCTs. Variations in primary endpoint, cancer stage, and ICI precluded meta-analysis. There is a significant gap in data from RCTs evaluating the efficacy of ICI in older patients with TNBC. The only FDA-approved ICI in TNBC, pembrolizumab, was shown in the early-stage setting to improve pathological complete response (pCR) and event-free survival (EFS) in older patients but was not statistically significant (KEYNOTE 522). In the metastatic setting, pembrolizumab may improve overall survival (OS) in older patients with combined positive score (CPS) ≥ 10 (KEYNOTE 355). Although atezolizumab in the metastatic setting showed initial promise in improving OS in the PD-L1 + population (IMPASSION 130), there was no difference in progression-free survival (PFS) nor OS between atezolizumab and placebo arms in IMPASSION 131. All studies had a limited number of patients 65 and older. These results underscore the need for further research on ICIs in older patients with TNBC.