Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Aim: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment paradigm in patients with non-small-cell lung cancer (NSCLC). However, progression patterns with immunotherapy are currently unclear and therapeutic options beyond resistance remain challenging. Methods: We reviewed advanced NSCLC patients between January 2016 and December 2019 who were treated with anti-PD-1/PD-L1 inhibitors in our center and identified those who developed disease progression. Later-line treatment strategies were collected and objective response rate, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Of the 118 patients, 46 (39.0%) showed oligoprogression and 72 (61.0%) showed systemic progression. No difference in progression patterns was observed between monotherapy and combination therapy. Systemic progression was strongly associated with never-smokers (51.4% vs. 21.7%, P = 0.001) and ECOG PS = 2 (13.9% vs. 2.2%, P = 0.048) at baseline. The distribution of progression sites was roughly similar between oligoprogression and systemic progression, and the most commonly affected anatomic site was lung (66.9%), followed by bone (12.7%) and lymph nodes (11.0%). For patients beyond first disease progression, checkpoint inhibitor-based combinations could lead to a significantly longer PFS2 compared with ICIs monotherapy (9.63 months vs. 4.23 months, P = 0.004, HR = 0.394, 95%CI: 0.174-0.893) and other therapy (9.63 months vs. 4.07 months, P = 0.046, HR = 0.565, 95%CI: 0.326-0.980). Median OS of the ICIs combination group was not reached but was significantly longer than other therapy group (NR vs. 14.37 months, P = 0.010, HR = 0.332, 95%CI: 0.167-0.661). Conclusion: Systemic progression occurs more frequently among NSCLC patients receiving ICIs. Checkpoint inhibitor-based combinations show favorable outcomes as subsequent treatment strategies after the failure of previous ICIs treatment.