Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group

TLDR

Recent trials demonstrate a significant overall survival benefit from postoperative cisplatin‑based chemotherapy in non‑small‑cell lung cancer patients. The Lung Adjuvant Cisplatin Evaluation aimed to identify treatment options and patient subgroups that derive greater benefit from postoperative chemotherapy by pooling individual patient data from the five largest cisplatin trials (4,584 patients). The authors analyzed interactions between patient subgroups or treatment types and chemotherapy effect on overall survival using hazard ratios and log‑rank tests stratified by trial, with a median follow‑up of 5.2 years. Pooled analysis of 4,584 patients showed that postoperative cisplatin‑based chemotherapy reduced the risk of death (HR 0.89, 5‑year absolute benefit 5.4%) with no heterogeneity across trials, but the magnitude varied by stage and was greater in patients with better performance status, while no significant interactions were found with drug type, sex, age, histology, surgery, radiotherapy, or cisplatin dose.

Abstract

Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non-small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy.Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial.With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin.Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.