DNA Repair by ERCC1 in Non–Small-Cell Lung Cancer and Cisplatin-Based Adjuvant Chemotherapy

TLDR

Adjuvant cisplatin‑based chemotherapy improves survival in completely resected non‑small‑cell lung cancer, yet no validated predictor of benefit exists. The study aimed to assess whether ERCC1 protein expression predicts benefit from cisplatin‑based adjuvant chemotherapy. ERCC1 expression was measured by immunohistochemistry in 761 tumors from the International Adjuvant Lung Cancer Trial, and overall survival was evaluated using a Cox model adjusted for clinical and pathological factors. Cisplatin‑based adjuvant chemotherapy significantly improved survival only in patients with ERCC1‑negative tumors (HR 0.65, 95 % CI 0.50–0.86), while no benefit was seen in ERCC1‑positive tumors (HR 1.14, 95 % CI 0.84–1.55); untreated ERCC1‑positive patients had longer survival than untreated ERCC1‑negative patients.

Abstract

Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy.We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors.Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009).Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.