A treatment-related death predictive score for treatment-naïve advanced non-small cell lung cancer

Combined chemotherapy with nivolumab and ipilimumab (NIC) improves survival outcomes in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). However, these patients have a higher incidence of treatment-related deaths (TRDs), especially due to NIC. This study aimed to devise a risk stratification score for selecting patients with lower or higher TRD risk.

A dataset from the JCOG2007 study was used, which compared NIC with combined chemotherapy with pembrolizumab (PC). The TRD score was built from an adaptive LASSO regression analysis.

The JCOG2007 study randomly assigned 295 patients to the PC (n = 147) and NIC (n = 148) arms, respectively. The TRD score was constructed for 124 patients who underwent NIC and had no missing covariates. The dichotomized TRD score was built and stratified all treated 290 (all enrolled 295) patients into 92 (92) high-risk and 198 (203) low-risk patients. No apparent differences in TRD incidence were observed in low-risk patients (2.2 % [0/92] with PC and 2.8 % [3/106] with NIC); however, this difference was noteworthy in high-risk patients (1.9 % [1/52] with PC and 20.0 % [8/40] with NIC). Of the 295 patients, the hazard ratios for death were 0.894 (0.553-1.444) in low-risk patients and that was 1.215 [0.696-2.122] in high-risk patients. Worse outcomes in the NIC arm were consistently observed for both immune-related adverse events (irAEs) and progression-free survival.

Although further validation studies with external data inside and outside Japan are required, the TRD score is a valuable tool for identifying patients with comparable toxicity-efficacy profiles among PC and NIC regimens.