Real-world treatment patterns and clinical outcomes for patients with deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC).

Abstract

e15550 Background: The 5-year follow up results of KEYNOTE-177 established pembrolizumab as a standard first-line treatment for dMMR mCRC, demonstrating improved response rates, progression-free survival (PFS) and tolerability over chemotherapy. Pembrolizumab became widely available as a first-line option in Australia following government reimbursement in August 2021. Real world treatment patterns and outcomes have not been reported. Methods: Consecutive patients with mCRC diagnosed between 1/8/2021 and 30/5/2025, and had dMMR as determined by immunohistochemistry test, were analysed, using data from TRACC, an Australian multi-site prospective registry. Clinicopathologic characteristics, treatment patterns and outcomes were examined. Results: From 32 sites, we identified 120 dMMR mCRC patients, of whom 109 (91%) received any systemic treatment. First-line treatment included pembrolizumab (n = 103, 94%), a clinical trial (n = 4, 4%), and chemotherapy (n = 2, 2%). Pembrolizumab treated patients had a median age of 75 years; 50% were also BRAF mutant. Further baseline characteristics are shown in the table. Median follow up was 25.8 months. The clinician-assessed response rate (partial or complete response) was 57%, with 17% of patients having progressive disease noted as best response. Median duration of therapy was 15.2 months. Discontinuation of pembrolizumab in 73 patients was due to progressive disease (37%), completion of 2 years of treatment (29%) and toxicity (15%). Median PFS was 37.9 months. Median overall survival (OS) was not reached, with a 12-month OS of 89% and 24-month OS of 73%. Conclusions: In this real-world population of dMMR mCRC patients, we noted older age, a greater proportion of BRAFV600E mutant, and poorer ECOG functional status compared with KEYNOTE-177. There has been rapid uptake of pembrolizumab as a new standard of care, with promising response rates, PFS and landmark OS achieved. Ongoing data collection are planned to explore predictors of immunotherapy response, and treatment and outcomes in the second line setting. Baseline characteristics. TRACC (n=103) KEYNOTE-177 pembrolizumab cohort (n=153) Age ≥ 65 years 76 (74%) 73 (48%) Male 44 (43%) 71 (46%) ECOG 0 40 (39%) 75 (49%) Charlson Comorbidity Index ≥4 56 (54%) - Primary tumor locationRight sideLeft sideOther / Unknown site 65 (63%)23 (22%)15 (15%) 102 (67%)46 (30%)5 (3%) Stage IV at diagnosis 53 (51%) 80 (52%) BRAF V600E mutant 51 (50%) 34 (22%) KRAS or NRAS mutant 15 (15%) 33 (22%) Site of metastasesLiverLungLymph nodesPeritoneum 40 (39%)15 (15%)44 (43%)27 (26%) -