Metastatic site and survival in colorectal cancer treated with pembrolizumab

In patients with mismatch repair–deficient metastatic colorectal cancer who were treated with pembrolizumab as a first- line therapy there is an association between metastatic site and survival outcome: a new study published on JAMA Network Open shows that liver versus non-liver metastasis was associated with significantly poorer progression-free survival, suggesting that metastatic site may have implications for treatment and survival.

This cohort study involved 41 older patients (mean age 81) with metastatic colorectal cancer with deficient DNA mismatch repair (dMMR) receiving first-line pembrolizumab (200 mg every 3 weeks); overall response rate was 49%, including 13 patients (32%) with complete responses. Median progression free survival was 21 months and liver as a site of metastasis was associated with significantly poorer progression-free survival versus non-liver metastasis: complete and partial responses were observed in 3 patients (21%) with liver metastasis versus 17 patients (63%) with non-liver metastases. Despite the advanced age of the patient population, the toxic effects were manageable and similar to those in younger patients. «The majority of colorectal cancers are sporadic and are observed in older patients, but published data for pembrolizumab as a first-line therapy for this tumor subset are limited to those in a single clinical trial, with younger patients and favorable performance status», authors say. «Older patients with cancer have often been undertreated and are underrepresented in clinical trial cohorts compared with younger patients, thus we aimed to investigate outcome with first-line pembrolizumab monotherapy in mostly older patients. Results show that the treatment was highly effective in routine clinical practice, despite the advanced age of the patients. The observation that a patient subset was free of disease after 3 or more years of follow-up suggests the likelihood of potential cure of metastatic disease. The finding that liver versus non-liver metastasis was associated with poorer survival in patients who received pembrolizumab suggests that metastatic site has implications for survival outcome and treatment», authors conclude.