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

Abstract 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.