Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer
Combined immune checkpoint inhibition with durvalumab plus tremelimumab may prolong overall survival in patients with advanced refractory colorectal cancer
A randomized phase 2 study evaluated the efficacy of combined immune checkpoint inhibition with durvalumab (PD‑L1 inhibitor) and tremelimumab (CTLA‑4 inhibitor) versus best supportive care (BSC) alone in patients with advanced refractory colorectal cancer (CRC). 180 patients were randomized 2:1 to the treatment or BSC arms; median overall survival (OS) was 6.6 months for durvalumab plus tremelimumab versus 4.1 months for BSC (hazard ratio 0.72, 90% CI 0.54–0.97). In microsatellite stable (MSS) patients with high plasma tumor mutation burden (TMB ≥28 variants/Mb), the greatest OS benefit was observed (HR 0.34, 90% CI 0.18–0.63). Grade 3/4 adverse events were more frequent in the treatment group (64% vs 20%). The study suggests that dual PD‑L1 and CTLA‑4 blockade may offer survival benefit in a subset of patients with MSS CRC.
Immune checkpoint inhibitors have limited efficacy in microsatellite stable colorectal cancer. This study identifies a potential therapeutic strategy—combining PD‑L1 and CTLA‑4 blockade—to extend survival in refractory MSS CRC, especially in patients with high tumor mutation burden, providing a new avenue for treatment optimization.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
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