Checkpoint inhibitors can be effective against microsatellite stable (MSS) colorectal cancer (CRC), but patients with liver metastases appear resistant to these drugs, according to a retrospective study published in JAMA Network Open.

The study authors noted that anti-PD-1/PD-L1 therapy has shown limited efficacy in MSS-CRC. The aim of the current study was to determine if the presence of liver metastases affects response to immunotherapy in this patient population.

The researchers retrospectively evaluated the medical records of 95 patients with metastatic MSS-CRC treated at City of Hope Comprehensive Cancer Center in Duarte, California, from Jan. 1, 2014, through Dec. 31, 2020.

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Patients had received at least 2 previous lines of treatment. Anti-PD-1/PD-L1 therapy included nivolumab, atezolizumab, pembrolizumab, and durvalumab.

At baseline, the patients’ median age was 55 years (range, 49-64 years), and 43.2% of patients were women. Sites of metastases included the lungs (69.5%), liver (56.8%), peritoneum (30.5%), distant lymph nodes (52.6%), brain (3.2%), and bone (10.5%). The median tumor mutational burden was 5.0.

The objective response rate (ORR) was 8.4% for the entire cohort. Patients without liver metastases had an ORR of 19.5%, but there were no responses in patients with liver metastases (P <.001).

The disease control rate was higher in patients without liver metastases as well (58.5% vs 1.9%; P <.001)

The median progression-free survival (PFS) was longer among patients without liver metastases than among those with it — 4.0 months and 1.5 months, respectively (P <.001).

The 6-month PFS was 36.6% in patients without liver metastases and 1.9% in patients with liver metastases.

“Findings of this cohort study suggest that patients with MSS metastatic colorectal cancer and without liver metastases may derive clinical benefits from checkpoint inhibitors, whereas the presence of liver metastases was associated with resistance,” the study authors wrote. “Further prospective studies are needed to investigate PD-1/PD-L1 inhibitors in patients with MSS metastatic colorectal cancer without liver metastases.”

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wang C, Sandhu J, Ouyang C, Ye J, Lee PP, Fakih M. 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. JAMA Netw Open. Published August 9, 2021. doi:10.1001/jamanetworkopen.2021.18416