The clinical value of local consolidative therapy for oligo-residual disease in PD-1/PD-L1 inhibitors-treated non-small cell lung cancer

Background: Few real-world studies exist regarding the clinical value of local consolidative therapy (LCT) for oligo-residual disease (ORD) in NSCLC patients treated with immune checkpoint inhibitors. Therefore, we retrospectively evaluated whether LCT could improve the prognosis of NSCL patients with ORD after effective first-line PD-1/PD-L1 inhibitors treatment. Methods: A total of 132 patients with metastatic NSCLC who had received first-line PD-1/PD-L1inhibitors-based systemic treatment and developed ORD (defined as residual tumors limited to three organs and five lesions) were included. The LCT group consisted of 41 patients received LCTs for oligo-residual lesions before treatment failure, and the remaining 91 patients, who did not receive local therapies, constituted the non-LCT group. The progression-free survival (PFS) and overall survival (OS) of the two groups were analyzed. Results: With a median follow-up of 12.0 months, 86 patients developed progressive disease and 42 patients died. Compared with the non-LCT group, LCT group exhibited significant longer progression-free survival (PFS) (median 11.0 vs. 7.0 months, P=0.017) and overall survival (OS) (median 26.0 vs. 17.0 months, P=0.003). Multivariable analysis demonstrated that LCT was an independent predictor of prolonged PFS (HR=0.606, 95% CI=0.370-0.964, P=0.035) and OS (HR=0.467, 95% CI=0.229-0.949, P=0.035). Subgroup analysis revealed that the dominant population considerably benefited from LCT in terms of PFS and OS included patients with 1-2 residual tumor sites (mPFS: 11.0 vs. 7.0 months, P=0.013; mOS: 23.0 vs. 17.0 months, P=0.018) and those with high PD-L1 expression (mPFS: 13.0 vs. 7.0 months, P=0.018; mOS: 34.0 vs. 16.0 months, P=0.030). In addition, the All-LCT group had significantly longer PFS (mPFS 16.0 vs. 7.0, P=0.002) and OS (mOS 28.0 vs. 17.0, P= 0.002) than did the non-LCT group. However, patients who received LCT to only some of their lesions had not experienced improvements in PFS (P=0.546) or OS (P=0.198). Conclusion: LCT may provide extra survival benefits among patients with oligo-residual NSCLC after effective first-line PD-1/PD-L1 inhibitors treatment, particularly in those patients with one or two residual lesions, high PD-L1 expression, or who had received LCT for all lesions. LCT may be a novel treatment option for this specific population.