Immune checkpoint inhibitor (ICI)-based treatment beyond progression with prior immunotherapy in patients with stage IV non-small cell lung cancer: a retrospective study

Background: Although immune checkpoint inhibitors (ICIs) provide unprecedented survival improvement for patients with advanced non-small cell lung cancer (NSCLC), disease progression inevitably occurs. After ICIs failure, limited data exist on whether ICI-based treatment beyond progression (TBP) may be beneficial to advanced NSCLC. This retrospective study aimed to evaluate the efficacy of this treatment approach in advanced NSCLC and identify potential beneficial factors.

Methods: Patients with stage IV NSCLC who received ICI-based treatment after the failure of prior PD-1/PD-L1 inhibitor treatments (monotherapy or combination therapy) between January 2016 and July 2020 were enrolled. Their clinical characteristics and treatment procedures were collected, and the follow-up would be performed.

Results: A total of 204 patients were included. All patients had disease progression after prior immunotherapy, with 49.5% (101/204) of patients presenting with new metastasis lesions and the rest 50.5% (103/204) of patients' progression on originate lesions. Within the entire cohort, the median progression-free survival (PFS) and median overall survival (OS) of ICI-based TBP with prior immunotherapy were 5.0 months (95% CI: 4.5-5.5 months) and 15.7 months (95% CI: 14.7-16.8 months), respectively. The objective response rate (ORR) and disease control rate (DCR) were 9.3% and 74.0%, respectively. According to the multivariate analysis, ICI-based combination therapy [PFS: hazard ratio (HR), 0.48, 95% confidence interval (CI): 0.28-0.84, P=0.011] (OS: HR, 0.44, 95% CI: 0.23-0.85, P=0.014), not having targetable gene alterations (PFS: HR, 0.56, 95% CI: 0.40-0.79, P=0.001) (OS: HR, 0.57, 95% CI: 0.37-0.87, P=0.009), and good response to prior immunotherapy (PFS: HR, 0.36, 95% CI: 0.24-0.53, P<0.0001) (OS: HR, 0.31, 95% CI: 0.19-0.52, P<0.0001) were independently associated with improved PFS and OS. Moreover, disease progression due to appearances of new metastasis (OS: HR, 0.56, 95% CI: 0.37-0.84, P=0.005) was only associated with better OS.

Conclusions: While the ORR in patients with advanced NSCLC receiving ICI-based TBP with prior immunotherapy was limited, the DCR was relatively high in our study which is encouraging. ICI-based treatment strategy may be a reasonable option for patients who progressed from prior immunotherapy. Further prospective studies on larger sample size are warranted.