Clin Transl Oncol. 2026 Jul 26. doi: 10.1007/s12094-026-04498-z. Online ahead of print.
ABSTRACT
PURPOSE: To explore whether adjuvant immunotherapy can improve postoperative prognosis for non-small cell lung cancer (NSCLC) patients harboring oncogenic driver alterations beyond EGFR and ALK, a population with unclear benefit.
METHODS: Main inclusion criteria included resected NSCLC, stage IB-IIIB, and oncogenic driver alterations of KRAS mutation, ROS1 fusion, RET fusion, HER2 mutation, NTRK fusion, BRAF V600E mutation, and MET exon 14 skipping mutation. The positive PD-L1 cut-off was 1%. Adjuvant immunotherapy would be administered for one year or up to 16 cycles. Disease-free survival (DFS) after surgery was the endpoint.
RESULTS: 190 patients with specific gene alterations were included, 25.8% of patients received adjuvant immunotherapy. The benefit from adjuvant immunotherapy in DFS was not observed in the overall population (hazard ratio [HR] 0.85, 95% confidence interval [CI 0.51-1.44, p = 0.551), while a numerical DFS benefit trend in the PD-L1-positive population was observed (HR 0.56, 95% CI 0.31-1.03, p = 0.059). After inverse probability of treatment weighting (IPTW) for the population with PD-L1 positivity who also received adjuvant chemotherapy, no statistical DFS benefit difference from adjuvant immunotherapy was observed between the KRAS (HR 0.29, 95% CI 0.10-0.88, p = 0.028) and non-KRAS mutation (HR 0.77, 95% CI 0.32-1.82, p = 0.549) subgroups (interaction p = 0.179), though with a marked numerical difference. Among the PD-L1-positive population, NSCLC harboring KRAS, MET exon 14 skipping, and BRAF V600E mutations showed a trend toward benefit from adjuvant immunotherapy, whereas NSCLC with HER2 mutation, RET fusion, and ROS1 fusion exhibited a weaker trend toward benefit.
CONCLUSIONS: Patients with NSCLC harboring driver oncogenes other than EGFR/ALK and positive PD-L1 showed a trend toward benefiting from adjuvant immunotherapy. Although no significant interaction was observed, KRAS-mutant NSCLC demonstrated numerically superior DFS benefit compared with non-KRAS-mutant NSCLC.
PMID:42503059 | DOI:10.1007/s12094-026-04498-z
