Differential predictive value of baseline tumor size according to PD-L1 expression in advanced NSCLC treated with immune checkpoint inhibitors.

[BACKGROUND] The predictive role of baseline tumor size (BTS) in advanced NSCLC treated with immune checkpoint inhibitors (ICIs) is unclear. We investigated its impact on ICI efficacy stratified by PD-L1 expression.

[METHODS] We retrospectively analyzed advanced NSCLC patients without driver mutations who received anti-PD-(L)1 therapy, with or without chemotherapy. The association between BTS and progression-free survival (PFS) was assessed according to tumor proportion score (TPS).

[RESULTS] A total of 423 patients were included, of whom 314 received ICI monotherapy, and 109 received chemoimmunotherapy. In the monotherapy group, patients with small tumors (<98 mm) exhibited significantly longer PFS compared to those with large tumors (≥98 mm) (7.1 vs. 2.3 months; p = 0.01). This trend was most pronounced in patients with TPS 1-49% receiving monotherapy (PFS: 4.9 vs. 1.3 months; p < 0.001). BTS was not significantly associated with PFS in the TPS ≥50% or <1% subgroups within the monotherapy cohort. However, in the chemoimmunotherapy group, PFS did not significantly differ between small and large tumors (7.1 vs. 5.5 months; p = 0.78). In the chemoimmunotherapy group, BTS significantly influenced PFS only in the TPS <1% subgroup (PFS 9.5 vs. 5.3 months; p = 0.03), but not in those with TPS ≥50% or 1-49%.

[DISCUSSION] BTS was a significant predictor of ICI monotherapy efficacy in patients with TPS 1-49%. Patients with large tumors and intermediate PD-L1 expression derived limited benefit from monotherapy, suggesting that chemoimmunotherapy may be more effective in this subgroup.