MSH2 and adjuvant cisplatin-based chemotherapy in non-small cell lung cancer

Abstract

CRA7502 Background: Adjuvant cisplatin-based chemotherapy improves survival among patients with non-small cell lung cancer. The human MutS homolog 2 (MSH2) protein is required to repair cisplatin-DNA lesions. Methods: We used immunohistochemistry to determine MSH2 expression in specimens from patients who had been enrolled in the International Adjuvant Lung Trial. The long-term (median follow-up 7.5 years) overall survival benefit was evaluated in a Cox model adjusted on clinical and pathological variables. Results: Among 673 evaluable tumors, 257 (38%) were MSH2 positive and 416 (62%) were MSH2 negative. The long-term survival benefit of chemotherapy was likely different according to MSH2 expression (test for interaction, P=0.06): chemotherapy compared with observation prolonged survival in the MSH2 negative group (adjusted hazard ratio for death, 0.76; 95%CI, 0.59 to 0.97; P=0.03), but not in the MSH2 positive group (adjusted hazard ratio for death, 1.12; 95%CI, 0.81 to 1.55; P=0.48). In the control arm, the adjusted hazard ratio for death associated with MSH2 positivity compared to MSH2 negativity was 0.66 (95%CI, 0.49 to 0.90; P=0.01). Among 658 patients with available excision repair cross-complementing group 1 (ERCC1) data, the benefit of chemotherapy decreased with the number of positive markers among MSH2 and ERCC1 (P=0.01). Chemotherapy compared with observation prolonged survival in the combined MSH2 negative/ERCC1 negative subgroup (adjusted hazard ratio for death, 0.65; 95%CI, 0.47 to 0.91; P=0.01). Conclusions: MSH2 appears to predict a long-term benefit from adjuvant cisplatin-based chemotherapy in patients with non-small cell lung cancer and may be combined with ERCC1. [Table: see text]