FOLFOX/XELOX improves survival, response rate in CRC patients with DDR-mutated tumour

Mutations affecting DNA damage response (DDR) are present in 22 percent of patients with metastatic colorectal cancer (CRC), reports a study. Initial treatment with fluoropyrimidine with oxaliplatin (FOLFOX/XELOX) improves overall survival in this population and is associated with a numerically higher response rate than fluoropyrimidine with irinotecan (FOLFIRI).

The authors carried out a retrospective analysis of 49 patients with metastatic CRC for whom treatment outcomes and results of comprehensive genomic profiling of tumours were available to determine whether DDR mutations could influence response to oxaliplatin and irinotecan-containing regimens.

Specimens with at least one pathogenic mutation involving BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L were categorized as DDR-mutated. Those without mutations were DDR-wild-type (WT).

The authors then compared the overall survival, disease control rate, and response rate between DDR-mutated and DDR-WT groups.

Eleven patients (22 percent) had mutations in DDR. First-line treatment with an oxaliplatin-containing regimen was administered to 33 patients (31 FOLFOX, two XELOX) and FOLFIRI to 16 patients.

Among patients with DDR mutations, first-line treatment with FOLFOX/XELOX compared with FOLFIRI resulted in a statistically significant improvement in median overall survival (3.4 vs 1.8 years; p=0.042) and numerically higher response rate (50 percent vs 33 percent; p=0.58).

In patients with DDR-WT tumours, no significant difference was seen in overall survival (2.4 vs 2.5 years; p=0.42), response rate, and disease control rate between the two regimens.