Treatment strategies based on different oligoprogressive patterns after immunotherapy failure in metastatic NSCLC

Oligoprogressive disease is recognized as the overall umbrella term; however, a small number of progressions on imaging can represent different clinical scenarios. This study aims to explore the optimal treatment strategy after immunotherapy (IO) resistance in advanced non-small-cell lung cancer (NSCLC), especially in personalized therapies for patients with different oligoprogressive patterns.

Based on European Society for Radiotherapy and Oncology/European Organization for Research and Treatment of Cancer consensus, metastatic NSCLC patients with cancer progression after IO resistance were divided into four patterns, repeat oligoprogression (REO, oligoprogression with a history of oligometastatic disease), induced oligoprogression (INO, oligoprogression with a history of polymetastatic disease), de-novo polyprogression (DNP, polyprogression with a history of oligometastatic disease), and repeat polyprogression (REP, polyprogression with a history of polymetastatic disease). Patients with advanced NSCLC who received programmed cell death-1/programmed cell death ligand-1 inhibitors between January 2016 and July 2021 at Shanghai Chest Hospital were identified. The progression patterns and next-line progression-free survival (nPFS), overall survival (OS) were investigated stratified by treatment strategies. nPFS and OS were calculated using the Kaplan-Meier method.

A total of 500 metastatic NSCLC patients were included. Among 401 patients developed progression, 36.2% (145/401) developed oligoprogression and 63.8% (256/401) developed polyprogression. Specifically, 26.9% (108/401) patients had REO, 9.2% (37/401) patients had INO, 27.4% (110/401) patients had DNP, and 36.4% (146/401) patients had REP, respectively. The patients with REO who received local ablative therapy (LAT) had significant longer median nPFS and OS compared with no LAT group (6.8 versus 3.3 months; p = 0.0135; OS, not reached versus 24.5 months; p = 0.0337). By contrast, there were no nPFS and OS differences in INO patients who received LAT compared with no LAT group (nPFS, 3.6 versus 5.3 months; p = 0.3540; OS, 36.6 versus 45.4 months; p = 0.8659). But in INO patients, there were significant longer median nPFS and OS using IO maintenance by contrast with IO halt treatment (nPFS, 6.1 versus 4.1 months; p = 0.0264; OS, 45.4 versus 32.3 months; p = 0.0348).

LAT (radiation or surgery) is more important for patients with REO while IO maintenance plays a more dominant role in patients with INO.