Immunotherapy beyond progression in patients with advanced non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) represent a great breakthrough in the treatment of advanced non-small cell lung cancer (aNSCLC). However, whether immunotherapy beyond progression (IBP) is effective for aNSCLC has yet to be established. Therefore, a retrospective clinical study was conducted to investigate the efficacy of IBP in patients with aNSCLC under real-world conditions.

A total of 125 Chinese patients with aNSCLC who experienced progressive disease (PD) after receiving monotherapy or combination therapy (combined with chemotherapy or/and antiangiogenic therapy) with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors between January 2015 and March 2019 were enrolled. Patients who were treated with ICIs for more than 6 weeks after PD were defined as IBP (n=39), while those who received ICI treatment for less than 6 weeks or discontinued it due to PD were defined as non-IBP (n=86). Patient clinical characteristics were evaluated. An optimization-based method was applied to balance the clinical baseline characteristics between the two groups.

In total population, the IBP group had longer overall survival (median OS, 26.6 vs. 9.5 months; HR, 0.40; 95% CI: 0.23-0.69; P<0.001) and progression-free survival (median PFS, 8.9 vs. 4.1 months; HR, 0.41; 95% CI: 0.26-0.65; P<0.001), compared with the non-IBP group. Despite no significant difference in objective response rate (ORR, 15.4% vs. 11.6%, P=0.560), disease control rate (DCR) was significantly higher in the IBP group (89.7% vs. 61.6%, P<0.001). After balancing baseline covariates, the IBP group also had longer OS (median: 26.6 vs. 10.7 months; HR, 0.40; 95% CI: 0.19-0.84; P=0.015) and PFS (median: 9.7 vs. 4.3 months; HR, 0.28; 95% CI: 0.15-0.51; P<0.001), with a benefit in either of patients previously treated with ICI monotherapy or in combination therapy and with non-response to the previously ICI.

IBP is associated with longer OS and PFS in patients with aNSCLC. Our findings may suggest new therapeutic options for patients with aNSCLC who experienced disease progression after initial immunotherapy.