First-Line Pembrolizumab in Older Patients With dMMR Metastatic Colorectal Cancer

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In a retrospective cohort study reported in JAMA Network Open, Saberzadeh-Ardestani et al found that first-line pembrolizumab was associated with clinically significant prolongation of survival outcomes in mostly older patients with mismatch repair–deficient (dMMR) metastatic colorectal cancer. Response rates and progression-free survival were poorer in patients with liver metastasis.  

Study Details

The study included data from 41 consecutive patients who received pembrolizumab at 200 mg every 3 weeks between April 2015 and January 2022 at Mayo Clinic sites and the Mayo Clinic Health System. The primary outcome measure was progression-free survival.

Key Findings

The median age of enrolled patients was 81 years (interquartile range [IQR] = 76–86 years) at treatment initiation. Among the 41 patients, 30 (73%) had a BRAF V600E mutation and 32 (78%) were classified as having sporadic tumors.

Median follow-up was 23 months (range = 3–89) months. The median number of treatment cycles was nine (IQR = 4–20 cycles).

Objective response was observed in 20 (49%) of 41 patients, with complete response in 13 (32%). Objective response was observed in 3 (21%) of 14 patients with liver metastasis vs 17 (63%) of 27 with nonliver metastases.  Median duration of response was 42 months (95% confidence interval [CI] = 9 months to not reached) among all responders. Among 13 patients with complete response, 5 remained free of disease for at least 3 years.

Median progression-free survival was 21 months (95% CI = 6–39 months) among all patients. Patients with liver metastases had significantly poorer median progression-free survival (6 months, 95% CI = 2–21 months) vs those with nonliver metastases (34 months, 95% CI = 14 months to not reached), with an adjusted hazard ratio of 3.40 (95% CI = 1.27–9.13, P = .01). Median overall survival among all patients was 36 months (95% CI = 14 months to not reached).

Treatment-related grade 3 or 4 adverse events occurred in eight patients (20%), most commonly pneumonitis and kidney failure, which occurred in two patients each. One treatment-related death occurred, due to myocarditis.

The investigators concluded, “This cohort study found a clinically significant prolongation of survival in older patients with dMMR metastatic colorectal cancer who were treated with first-line pembrolizumab in routine clinical practice. Furthermore, liver vs nonliver metastasis was associated with poorer survival in this patient population, which suggests that the metastatic site has implications for survival outcome.”

Frank A. Sinicrope, MD, of the Division of Oncology, Mayo Clinic & Mayo Comprehensive Cancer Center, Rochester, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit