# The efficacy analysis of immunotherapy rechallenge after progression from first-line chemo-immunotherapy in advanced non-small cell lung cancer

## TL;DR

This study finds that reusing immunotherapy after it initially failed in lung cancer patients can improve survival, especially when combined with anti-angiogenesis drugs.

## Contribution

The study evaluates the efficacy of immunotherapy rechallenge in advanced NSCLC after first-line chemo-immunotherapy and identifies factors influencing outcomes.

## Key findings

- Immunotherapy rechallenge achieved a median overall survival of 19.47 months and progression-free survival of 7.10 months.
- Adding anti-angiogenesis drugs significantly improved progression-free survival compared to immunotherapy alone.
- Prior immunotherapy response and smoking status were independent prognostic factors for progression-free survival.

## Abstract

Combining immune checkpoint inhibitors (ICI) with chemotherapy has been established as the standard first-line (1 L) treatment for advanced non-small cell lung cancer (NSCLC). However, the optimal second-line (2 L) treatment following 1 L chemo-immunotherapy remained controversial.

Patients with advanced NSCLC who progressed following 1 L chemo-immunotherapy and continued to receive ICI as 2 L therapy were enrolled in the study. These patients were divided into two groups according to the therapeutic modality: chemo-immunotherapy plus anti-angiogenesis therapy group (CIA group) and chemo-immunotherapy group (CI group). Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) to minimize selection bias before comparative analyses. The efficacy of immunotherapy rechallenge combination therapy was evaluated based on overall survival (OS) and progression-free survival (PFS). Cox proportional hazards regression analyses were applied to determine predictive factors independently associated with survival outcomes.

A total of 101 patients were enrolled in this study, 45 patients were enrolled in CIA group, and those who didn’t receive anti-angiogenesis drugs were defined as CI group (n = 56). Overall, Immunotherapy rechallenge reached a median OS of 19.47 months and median PFS of 7.10 months. The CIA group showed significantly longer PFS than the CI group (11.49 vs. 6.06 months, p = 0.03). Similar results in PFS were observed in the study cohorts balanced with IPTW (11.49 vs. 6.89, p = 0.01). Multivariate analyses revealed that prior immunotherapy response and smoking status could be independent prognostic factors for PFS.

Immunotherapy rechallenge could bring survival benefits following progression under chemo-immunotherapy, especially those who responded to prior immunotherapy. Additionally, the use of anti-angiogenesis drugs could significantly improve the clinical response of immunotherapy rechallenge.

The online version contains supplementary material available at 10.1186/s12865-026-00800-4.