Combination of hepatic artery infusion chemotherapy and PD1 immune checkpoint inhibitor improve survival in patients with KRAS-mutated unresectable colorectal liver metastases: A propensity score matching study.

Objective: This study examined the effect of hepatic arterial infusion chemotherapy (HAIC) plus programmed death 1 inhibitors (HAICPs) in patients with unresected colorectal cancer liver metastases (UCRLM) with and without KRAS mutations.

Materials and methods: We retrospectively collected data from patients with UCRLM, who received HAIC with HAICP or HAIC alone (oxaliplatin plus fluorouracil), including information on KRAS status (mutated, MUT; wild-type, WT) from a multicenter institutional database. Propensity score matching (PSM) was performed. The associations of KRAS status, treatment, and clinicopathological features with outcomes were determined. Confounding factors were adjusted using the Cox proportional hazard model.

Results: A total of 668 patients (414 KRAS-WT, 254 MUT) were followed for a median of 4.6 years post-HAIC. Fifty-five percent received HAICP. Before PSM, patients in the HAICP group exhibited a significantly higher CEA level (P = 0.014), more tumor nodules (P = 0.012), lower clinical risk score (P = 0.009), and fewer extrahepatic metastases (P = 0.017). After PSM analysis, 260 pairs of patients were established. The 5-year progression-free survival (PFS) for patients treated with HAICP versus HAIC was 36% and 31%, respectively (hazard ratio, 0.64; 95% CI, 0.48-0.85; P = 0.008). The 5-year overall survival (OS) for patients treated with HAICP versus HAIC was 72% and 64%, respectively (hazard ratio, 0.44; 95% CI, 0.32-0.63; P < 0.001). In KRAS-WT tumors, the 5-year survival was 79% and 61% for patients treated with HAICP versus HAIC (P < 0.001), respectively. In KRAS-MUT tumors, the 5-year survival was 68% and 52% for patients treated with HAICP versus HAIC (P < 0.001), respectively.

Conclusion: The combined application of HAICP is an effective regimen for treating patients with UCRLM. HAICP shows superior survival independent of KRAS mutation. In addition, HAICP ameliorates the poor survival observed among KRAS-MUT UCRLM cases.