The role of immunotherapy and chemotherapy combinations in TKI-resistant EGFR-mutant non-small cell lung cancer: insights from real-world evidence.

PURPOSE

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment for advanced -mutant non-small cell lung cancer (NSCLC). Despite this, most patients experience tumor progression. The optimal immunotherapy (IO)-based strategy and its timing after EGFR-TKI failure remains under debate.

MATERIALS AND METHODS

A retrospective analysis was performed to assess the outcomes for patients with -mutant NSCLC who were treated with either IO alone or in combination with chemotherapy (C/T) following disease progression. Data from January 2014 to December 2022 at Taipei Veterans General Hospital were reviewed. The Kaplan-Meier method was used to evaluate overall survival (OS) and time to treatment failure (TTF), while a Cox proportional hazards model evaluated the impact of clinical factors on survival.

RESULTS

This study enrolled 107 patients with advanced -mutant NSCLC, all of whom had previously been treated with first- to second-generation EGFR-TKIs. The IO alone group included 33 patients, while 74 patients were in the IO combined with chemotherapy (IO+C/T) group. The median number of prior treatment lines before immunotherapy was 2. The IO+C/T group demonstrated a trend toward longer OS compared to the IO alone group (OS: 20 vs. 16 months, P=0.70). Patients with more than four lines of treatment before IO-based therapy had significantly worse OS (6 vs. 29 months, P<0.001) and TTF (2 vs. 5, P=0.018) than those less than 4 lines of treatment. Multivariate analysis revealed that patients who had undergone more than 4 lines of treatment before IO-based therapy had poorer OS (HR 2.21, 95% CI 1.16-4.21, P=0.01) and TTF (HR 1.89, 95% CI 1.11-3.19, P=0.019) compared to those with fewer than 4 lines of treatment. The HRs for OS were 4.32 (95% CI 1.95-9.61, P<0.001) for patients with more than 4 lines of treatment and 2.05 (95% CI 1.04-4.05, P=0.038) for those with 2-4 lines of treatment, in comparison to patients who had 0-1 lines of treatment.

CONCLUSION

This study highlights the potential benefits of early initiation of IO-based regimens in advanced -mutant NSCLC following EGFR-TKI failure. Combination therapy with chemotherapy showed a trend toward improved survival compared to IO monotherapy, although not statistically significant. Moreover, poorer outcomes associated with multiple prior treatments underscore the importance of timely implementation of IO-based strategies to optimize clinical benefit in this patient population.