Liao WY, et al. - In this prospective evaluation of the impact of single nucleotide polymorphisms (SNPs) of ERCC1, ERCC2, XRCC1, and XRCC3 on first-line pemetrexed/platinum treatment outcome in advanced non-squamous non-small-cell lung cancer (NSCLC) patients, it was shown that a combination of ERCC1 and ERCC2 polymorphisms may predict overall survival (OS) among pemetrexed/platinum treated advanced non-squamous NSCLC patients.

• Researchers used TaqMan SNP Genotyping Assays to perform genotyping of 6 SNPs in 4 DNA repair genes in 58 patients treated with first-line pemetrexed/platinum.

• Significant association of the wild-type ERCC1 8092 (C/C) with a better objective response was observed, as compared to the variant genotypes (C/A + A/A) (48% vs 10%, P = 0.005).
• Significantly better overall survival (OS) for individuals with a wild-type genotype of ERCC1 Asn118Asn, ERCC1 C8092A and ERCC2Asp312Asn vs those with a heterozygous or homozygous variant genotype was found in the multivariate Cox proportional hazards model.
• On the other hand, findings demonstrated that the heterozygous variant genotype of ERCC2 Lys751Gln was associated with better OS than that of the wild-type genotype.
• Further exploration of the combined impact of SNPs on OS suggested a significant allele/dose-dependent trend toward decreasing OS in patients with an increasing number of unfavorable alleles among 4 SNPs in ERCC1 and ERCC2.
• In addition, significantly longer median OS was reported among patients with two or three unfavorable alleles (30.1 and 30.5 months, respectively) vs patients with 4 unfavorable alleles (11.8 months, log-rank test for trend, P=0.001).