Favorable clinical impact of histological subtype with non-small cell carcinoma-not otherwise specified in patients with non-small cell lung cancer receiving immune checkpoint inhibitors

BACKGROUND: Non-small cell lung cancer (NSCLC) is diagnosed using small biopsy samples obtained by bronchoscopy or transthoracic lung core biopsy, and treated with immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and programmed cell death protein ligand-1 (PD-L1) inhibitors, as the first-line therapy. However, the clinical benefits of first-line PD-1/PD-L1 inhibitors in non-small cell carcinoma-not otherwise specified (NSCC-NOS) remain unclear. This study aimed to clarify the clinical efficacy of first-line PD-1/PD-L1 inhibitors in patients with NSCC-NOS. METHODS: We retrospectively enrolled patients with recurrent or unresectable advanced NSCLC treated with first-line PD-1/PD-L1 inhibitors, with or without chemotherapy, at three medical institutions. We adjusted for patient characteristics using propensity score matching (PSM) and analyzed the impact of the histological subtype, NSCC-NOS, on survival outcomes in patients with NSCLC treated with immunotherapy. RESULTS: Of the 312 eligible patients, 42 (13.5%) had a histological subtype of NSCC-NOS. Significantly more patients had PD-L1 ≥ 50% in the NSCC-NOS group than in the Non NSCC-NOS group (P = 0.01). After PSM, 41 patients with NSCC-NOS and 123 with other histological subtypes (Non NSCC-NOS) were analyzed. The median progression-free survival (PFS) and the median overall survival (OS) of patients with NSCC-NOS were significantly longer than those of patients with Non NSCC-NOS, respectively (median PFS: 14.8 vs. 6.1 months, P < 0.01; median OS: 33.4 vs. 15.1 months, P = 0.04, log-rank test). CONCLUSIONS: NSCC-NOS is a histological subtype that is highly responsive to first-line PD-1/PD-L1 inhibitors with or without chemotherapy.