Real-world effectiveness and safety of treatment strategies for unresectable, driver-negative Stage III NSCLC: A retrospective multicentre study.

Concurrent or sequential chemoradiotherapy followed by immunotherapy (CCRT/SCRT→IO), known as the PACIFIC regimen, is the standard of care for unresectable, driver gene-negative Stage III non-small cell lung cancer (NSCLC). However, in real-world practice, some patients cannot proceed to immunotherapy due to toxicity, declining performance status, or disease progression. This multicenter retrospective study included 960 patients from 14 Chinese institutions (2011-2023) to evaluate the efficacy and safety of alternative regimens. Patients were stratified into five groups. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate, disease control rate, duration of response, and immune-related adverse events (irAEs). Inverse probability treatment weighting was used to adjust for baseline differences. Among 911 evaluable patients, weighted median PFS was 21.7 months for (IO + CCRT/SCRT) → IO, 16.8 for (IO + Chemo) → IO, 25.8 for CCRT/SCRT → IO, 7.1 for chemotherapy alone, and 14.8 for CCRT/SCRT. Median OS was not reached in the (IO + CCRT/SCRT) → IO group and ranged from 31.1 to 58.3 months in others. No significant differences in PFS or OS were found between (IO + CCRT/SCRT) → IO and CCRT/SCRT → IO. Pneumonitis occurred most frequently in the CCRT/SCRT → IO group. Early initiation of IO did not significantly increase irAE risk. These findings support early integration of IO with chemoradiotherapy and maintenance IO as a viable option for unresectable Stage III NSCLC.