Abstract
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.
Highlights
Advances in immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1) have dramatically changed the treatment landscape for non-small cell lung cancer (NSCLC), providing durable clinical response in a subset of patients[1,2]
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 overall survival (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)
Summary
Advances in immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1) have dramatically changed the treatment landscape for non-small cell lung cancer (NSCLC), providing durable clinical response in a subset of patients[1,2]. A clear definition is not reported, oligoprogression has been proposed and described as a special clinical situation where a limited number of metastatic tumor sites have progressed. It is a relatively new concept denoting anatomically restricted tumor progression in patients. Local therapies including stereotactic body radiotherapy (SBRT), ablation, and surgical operations are applied as the management of oligoprogression. This may allow the continuing use of systemic treatments and result in a prolonged response[5]. The progression patterns of immunotherapy and their correlations with clinical parameters remain to be explored
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