Concurrent immunotherapy improves progression-free survival but increases toxicity in unresectable stage III NSCLC

The PACIFIC trial established consolidation immunotherapy (IO) after concurrent chemoradiotherapy as the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC) by improving survival. However, the optimal timing of IO remains debated. This study analyzes the survival benefits and risks of IO concurrent with radiotherapy (RT) versus IO following RT.

A systematic search of multiple databases identified studies comparing IO concurrent with RT and IO following RT in unresectable stage III NSCLC. Data on overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were analyzed using the "meta" package in R, along with a single-center cohort study.

The meta-analysis showed improved PFS with IO concurrent with RT, with significant differences at 1 year (69.5 % vs 57.6 %) and 1.5 years (56.3 % vs 45.7 %). OS was slightly better with IO following RT, with fewer severe AEs (≥grade 3: 52.6 % vs 37.2 %). A single-center cohort validated superior PFS for the concurrent group (HR = 2.039, 95 % CI: 1.014-4.322, P = 0.046). Shorter intervals between RT and IO were associated with better PFS in the following group (HR = 1.002, 95 % CI: 1.001-1.003, P = 0.002).

Concurrent IO with RT during chemoradiotherapy significantly improved PFS in unresectable stage III NSCLC, though OS did not benefit due to a higher incidence of severe AEs. Earlier IO initiation after RT was associated with better PFS. Our findings suggest the potential benefits of concurrent IO for selected patients.