Adding immune checkpoint inhibitors to chemotherapy in elderly cancer patients: Beneficial for many but not all?

Abstract

Introduction: The strategic addition of immune checkpoint inhibitors (ICIs) to chemotherapy (CT) offers a potential paradigm shift in the treatment of elderly cancer patients. This systematic review evaluates the impact of ICIs combined with CT on the overall survival (OS) of patients aged 65 and older.

Material and methods: Using the terms "immune checkpoint inhibitors" and (PD-1 or PD-L1 or CTLA-4) and ("cancer" or "carcinoma") and ("elderly" or "older" or "65 years" or "70 years"), we searched PubMed, Embase, and the Cochrane Library through March 2024. We selected only English language, phase II-III randomized controlled trials comparing first-line CT + ICIs vs. CT alone for metastatic cancers, with subgroups reporting outcomes of elderly patients (according to the authors' cutoff of at least 65 years). Hazard ratios (HR) for OS with relative 95% confidence intervals (95%CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studiesResults:The study synthesizes data from 46 phase III randomized controlled trials, focusing on first-line treatments for metastatic cancers, where ICIs plus CT are compared against CT. The meta-analysis reveals that the combination therapy significantly improves OS in certain cancer types like lung cancers (HR=0.79, 95%CI 0.73-0.86; P<0.01), esophageal (HR=0.68, 95%CI 0.6-0.77; P<0.01) and gastric carcinomas (HR=0,8, 95%CI 0.63-0.88; P<0.01). In other cancers, evidence is less strong (e.g, gynecological, breast, genitourinary, head and neck, and skin cancers).

Conclusions: These findings suggest that while the addition of ICIs can enhance survival outcomes in a subset of elderly cancer patients, its efficacy is highly contingent upon the cancer type and the specific patient's health profile.

Keywords: chemotherapy; elderly cancer patients; immune checkpoint inhibitors; meta-analysis; overall survival.