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Comparative Effectiveness of Biomarkers for Identifying Responders to ICIs vs. Chemotherapy in Metastatic Colorectal Cancer

High microsatellite instability (MSI-H) based on next-generation sequencing (NGS) was effective for identifying patients with metastatic colorectal cancer (MCRC) with favorable outcomes on first-line immune checkpoint inhibitors (ICIs) versus chemotherapy, a comparative effectiveness study shows.

The study included 1 cohort of patients with MSI-H MCRC who received first-line ICIs or chemotherapy and a second cohort who received ICIs in any line of therapy (LOT) for biomarker examination. The main outcomes were time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS).

At 280 U.S. academic or community-based cancer clinics between Mar. 2014 and Dec. 2021, the investigators found: “A total of 138 patients (median age, 67.0 years [IQR, 56.2-74.0 years]; 73 [52.9%] female) with MSI-H MCRC received first-line ICIs or chemotherapy. A total of 182 patients (median age, 64.5 years [IQR, 55.2-72.0]; 98 [53.8%] female) received ICIs in any LOT. Patients receiving first-line ICIs vs chemotherapy had longer TTNT (median, not reached [NR] vs 7.23 months [IQR, 6.21-9.72 months]; adjusted hazard ratio [AHR], 0.17; 95% CI, 0.08-0.35; P < .001), PFS (median, 24.87 months [IQR, 19.10 months to NR] vs 5.65 months [IQR, 4.70-8.34 months]; AHR, 0.31; 95% CI, 0.18-0.52; P < .001), and OS (median, NR vs 24.1 months [IQR, 13.90 months to NR]; HR, 0.45; 95% CI, 0.23-0.88; P = .02). MSI added to [mismatch repair deficiency] better anticipated TTNT and PFS in patients receiving ICIs than [mismatch repair deficiency] alone. The same was not observed when [mismatch repair deficiency] evaluation was added to MSI.”

Source: JAMA Network Open