PD-1 inhibitors + chemo improve OS, PFS, ORR in first-line advanced ESCC; benefit limited in PD-L1 CPS <1

This systematic review and meta-analysis evaluated the efficacy and safety of PD-1 or PD-L1 inhibitors plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). The analysis included 8 randomized controlled trials, enrolling a total of 4702 patients (2529 in the PD-1 inhibitor plus chemotherapy group and 2173 in the chemotherapy alone group). Compared to conventional chemotherapy, the combination therapy significantly improved overall survival (hazard ratio = 0.68, 95% confidence interval: 0.63-0.74; P < .00001), progression-free survival (hazard ratio = 0.62, 95% CI: 0.58-0.66; P < .00001), and objective response rate (relative risk = 2.03, 95% CI: 1.80-2.29; P < .00001). The analysis found that PD-1 inhibitors were not associated with statistically lower incidences of treatment-related adverse events (TRAEs) or grade 3 to 5 TRAEs. Subgroup analyses indicated that factors such as advanced age, metastatic status, number of metastatic organs, or presence of liver metastases did not significantly influence the efficacy of the PD-1 inhibitor-based therapy. However, a limited benefit was observed in the subgroup of patients with a programmed death-ligand 1 (PD-L1) combined positive score < 1. The authors conclude that the combination demonstrates superior efficacy, with universal benefit for elderly and metastatic patients without increased adverse risks, but note that patients with PD-L1 CPS <1 may have restricted clinical benefit, highlighting a need for more precise predictive markers.

For people with advanced esophageal cancer, a new first-line treatment combining immunotherapy (called a PD-1 inhibitor) with chemotherapy is a significant step forward. This analysis of over 4,700 patients from eight major trials shows the combination is clearly more effective than chemotherapy alone. It helps patients live longer, delays the cancer's progression, and is more than twice as likely to shrink tumors. Importantly, the risk of serious treatment-related side effects was not statistically higher than with chemo alone. The benefits were widespread. Older patients and those whose cancer had spread, even to the liver, saw similar improvements. But there's one important exception: patients whose tumors have very low levels of a protein called PD-L1 (specifically, a combined positive score of less than 1) may get only a limited benefit from adding the immunotherapy. This means that while this combo is a powerful new option for most, doctors need better tests to identify everyone who will respond, so no one misses out on the right treatment.