Oligo-Residual Disease in PD-1/PD-L1 Inhibitors Treated Metastatic Non-Small Cell Lung Cancer: Incidence, Pattern of Failure and Clinical Value of Local Consolidative Therapy

Abstract

Growing numbers of clinical trials are testing the efficacy of incorporating local therapy into programmed death receptor (ligand) 1 (PD-1/PD-L1) inhibitors in metastatic non-small cell lung cancer (NSCLC), but the optimal timing and patient selection are still controversial. We aimed to examine the patterns of maximum tumor response and treatment failure in PD-1/PD-L1 inhibitor-treated NSCLC, and explore the potential clinical value of local consolidative therapy (LCT) in those with oligo-residual disease (ORD). Metastatic NSCLC treated with PD-1/PD-L1 inhibitors in three academic centers from May 2018 to December 2021 were retrospectively reviewed and those derived clinical benefit, defined as having objective response or durable stable disease lasting≥6months, were finally enrolled. Patterns of tumor response and treatment failure were extensively analyzed. ORD was defined as residual tumor distribution limited to 3 organs and 5 lesions, otherwise was defined as multiple residual disease (MRD). Local therapies targeting the residual tumor lesions performed after PD-1/PD-L1 inhibitors initiation and before initial disease progression, were considered as LCT. The primary endpoints were the overall survival (OS) and progression-free survival (PFS). Of the 318 patients enrolled, ORD and MRD were documented in 122 (38.4%) and 196 (61.6%) patients, respectively. Those who developed ORD had a significantly longer OS than those with MRD (p = 0.006). The median time to best response was 4 months and more than 50% of the initial disease progression developed only from the residual tumor lesions, providing the preliminary rationale of LCT. Among the 122 patients with ORD, those receiving LCT (n = 39) had significantly longer PFS (p = 0.04) and OS (p<0.001) than those without LCT. Moreover, LCT remained one of the independent predictors of improved PFS and OS after Cox analyses. Local consolidative therapy seems to be feasible and may provide extra survival benefit for metastatic NSCLC patients with oligo-residual disease after PD-1/PD-L1 inhibitor treatment.