258P Immune checkpoint inhibitors addition to chemotherapy in older patients with metastatic triple-negative breast cancer: A systematic review and meta-analysis

The therapeutic approach for metastatic triple-negative breast cancer (mTNBC) has always been challenging, given its typically aggressive natural history and the lack of possible actionable targets. The introduction of Immune Checkpoint Inhibitors (ICIs) is reshaping the clinical management of this disease; nevertheless, its role is still controversial when dealing with populations characterized by higher heterogeneity. Due to the epidemiological transition, older patients, burdened by vulnerability and frailty, will constitute an ever-increasing proportion of cancer patients. Therefore, this analysis aimed to determine the efficacy of this emerging therapy in older patients with mTNBC, also focusing on the subgroup expressing PD-L1. We systematically searched PubMed, Embase, Web of Science, and Cochrane CENTRAL for eligible trials of ICIs addition to chemotherapy compared to chemotherapy alone for mTNBC patients aged ≥65 years. Progression-free survival (PFS) and overall survival (OS) were measured as primary outcomes. Sub-analyses based on PD-L1 expression were also performed. Three randomized controlled trials involving 471 older patients were included. The addition of ICIs to chemotherapy resulted in a better PFS compared with chemotherapy alone (hazard ratio [HR]: 0.70 [0.55-0.89], p= 0.004) in the overall population and in the PD-L1-positive patients (HR: 0.62 [0.46-0.83], p= 0.001). In contrast, the use of ICIs did not significantly improved OS in the overall population (HR: 0.82 [0.65-1.04], p= 0.334) or in PD-L1 positive-patients (HR: 0.75 [0.54-1.03], p= 0.573).Table: 258PTrialHazard Ratio [95% CI]Weight %PFSIMpassion1300.69 [0.51-0.94]60.84Keynote3550.72 [0.49-1.05]39.160.70 [0.55-0.89]Heterogeneity: χ2 = 0.03 (df =1), p= 0.864; I2 = 0% Test for overall effect: z = 2.91, p= 0.004PFS / PD-L1+IMpassion1300.48 [0.30-0.79]36.17IMpassion1310.80 [0.41-1.58]18.63Keynote3550.69 [0.45-1.07]45.200.62 [0.46-0.83]χ2 = 1.86 (df =2), p= 0.395; I2 = 0% z = 3.20, p= 0.001OSIMpassion1300.92 [0.67-1.26]54.64Keynote3550.73 [0.56-1.12]45.360.82 [0.65-1.04]χ2 = 0.94 (df =1), p= 0.334; I2 = 0%z = 1.58, p= 0.114OS / PD-L1+IMpassion1300.67 [0.40-1.13]38.12Keynote3550.81 [0.54-1.22]61.880.75 [0.54-1.03]χ2 = 0.32 (df =1), p= 0.573; I2 = 0%z = 1.73, p= 0.084 Open table in a new tab ICIs + chemotherapy significantly improved PFS in older patients with mTNBC, especially in PD-L1-positive subgroup, while no statistically significant association was found with OS. Further studies are needed to investigate the efficacy and safety of ICIs + chemotherapy in late life.