Event-free survival as a predictor of overall survival and recurrence burden of patients with non–small cell lung cancer receiving neoadjuvant therapy

OBJECTIVES:Event-free survival (EFS) has replaced overall survival (OS) as a primary endpoint in many recent and on-going clinical trials. This study aims to examine the correlation between real-world EFS (rwEFS) and OS and to assess the clinical and economic burden associated with disease recurrence among patients with resected, stage II-III non-small cell lung cancer (NSCLC) received neoadjuvant therapy in the US. METHODS:This retrospective study used the SEER-Medicare database (2007-2019) to identify patients with newly diagnosed, resected, stage II-IIIB (N2) NSCLC received neoadjuvant therapy. The correlation between rwEFS and OS was assessed using the normal scores rank correlation and landmark analysis. OS, all-cause healthcare resource utilization (HCRU) and costs, and NSCLC-related HCRU and costs were compared between patients with and without recurrence. RESULTS:A total of 221 patients met the eligibility criteria (median follow-up time from neoadjuvant treatment initiation: 32.7 months). The mean age was 72.1 years, and 57.0% of patients were male. rwEFS and OS are positively and significantly correlated (0.68; 95% CI: 0.52-0.79). Patients with recurrence had significantly shorter median OS (19.3 months vs. 116.9 months), 4.59 times increased risk of death (95% CI: 2.56, 8.26), and significantly higher all-cause and NSCLC-related HCRU and costs (adjusted mean monthly costs per patient difference: $5,758 and $3,187, respectively (all p<0.001). CONCLUSIONS:These findings help validate EFS as a clinically meaningful endpoint and strong predictor for OS and highlight the need for additional novel therapies that may delay or prevent recurrence in resectable stage II and III NSCLC.