Clinical Response to Immunotherapy Targeting Programmed Cell Death Receptor 1/Programmed Cell Death Ligand 1 in Patients With Treatment-Resistant Microsatellite Stable Colorectal Cancer With and Without Liver Metastases

Key Points Question Is immunotherapy targeting programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) associated with the presence of liver metastasis at the time of therapy and outcomes among patients with treatment-resistant microsatellite stable (MSS) metastatic colorectal cancer? Findings This cohort study included 95 patients with MSS metastatic colorectal cancer. Patients without liver metastases had a significantly superior objective response rate (19.5% vs 0) and median progression-free survival (4.0 vs 1.5 months) compared with patients with liver metastases; multivariate analysis revealed that the presence of liver metastases was an independent prognostic factor associated with poor outcome of PD-1/PD-L1 therapy. Meaning This cohort study suggests that PD-1/PD-L1 inhibitors should be reinvestigated in prospective trials in patients with MSS metastatic colorectal cancer without liver involvement.
Importance Microsatellite stable (MSS) metastatic colorectal cancer has been historically characterized as resistant to immunotherapy. Recent studies have demonstrated limited clinical activity of programmed cell death receptor 1/programmed death ligand 1 (PD-1/PD-L1) targeting in MSS metastatic colorectal cancer. The association of metastatic disease in the liver with treatment response has not been fully investigated. Objective To investigate the association of liver metastases with response to PD-1/PD-L1–targeting therapy in MSS metastatic colorectal cancer. Design, Setting, and Participants This single-center retrospective cohort study evaluated clinical responses to PD-1– or PD-L1–targeting therapy, with or without other investigational agents, in patients with MSS metastatic colorectal cancer and disease progression after standard of care therapy from January 1, 2014, to December 31, 2020. Main Outcomes and Measures Objective response rate (ORR) and progression-free survival (PFS), measured from initiation of PD-1/PD-L1–targeting therapy. Results Ninety-five patients with MSS metastatic colorectal cancer were identified (54 men [56.8%]; median age, 55 [interquartile range (IQR), 49-64] years). The overall ORR was 8.4% (8 of 95 patients). Eight of 41 patients without liver metastases achieved an ORR of 19.5%, and no response was observed in 54 patients with liver metastases. The disease control rate was 58.5% (24 of 41) in patients without liver metastasis and 1.9% (1 of 54) in patients with liver metastasis. Patients without liver metastases at the time of PD-1/PD-L1–targeting treatment had a superior median PFS compared with patients with liver metastases (4.0 [IQR, 2.0-7.5] vs 1.5 [IQR, 1.0-2.0] months; P
This cohort study analyzes the association of metastatic disease pattern with response to programmed cell death receptor 1/programmed cell death ligand 1–targeting therapy in patients with treatment-resistant microsatellite stable metastatic colorectal cancer.