Analysis of ICIs alone or in combination rechallenged outcomes after progression from first-line ICIs plus chemotherapy in patients with advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) plus chemotherapy have become the standard of care for first-line treatment of advanced non-small cell lung cancer (NSCLC) with EGFR/ALK negative. However, there is no clear second-line treatment option after first-line treatment failure. To investigate the efficacy and safety of ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC. We retrospectively analyzed the cases of patients who received ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC at Hunan Cancer Hospital between January 2020 and May 2024. We evaluated the effects of continued immunotherapy on patients' objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events after first-line treatment progression, and analyzed the relationship between outcomes and clinical characteristics. A total of 154 patients were included, with 146 patients developing resistance, 8 patients showing no progression. The ORR was 16.44%, the DCR was 68.49%, and the median PFS was 4.6 months. Patients treated with the new immune drug therapy had longer PFS than those treated with the original immunotherapy (5.0 months vs. 3.7 months, p = 0.0438). The PFS in patients receiving ICIs plus targeted therapy was significantly longer than that in patients who receiving ICIs alone, chemo-ICIs plus targeted therapy and ICIs plus chemotherapy (chemo-ICIs) (5.7 months vs. 3.6 months vs3.2 months vs. 2.9 months, p = 0.0086). Multivariate analysis showed that treatment regimen was a risk factor for immune rechallenge PFS, but there was no statistical correlation between gender, age, smoking history, pathological type, intermittent treatment or first-line drug resistance and immune rechallenge PFS. Our findings suggest that selecting ICIs plus targeted therapy may improve PFS in patients with advanced NSCLC after first-line chemo-ICIs progression. while replacement with new BSAb/PD-1 may be more beneficial to patients. However, there is a lack of large sample randomized controlled studies and evidence-based medical evidence, and more clinical studies are needed to further confirm.