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Impact of Subsequent Treatment on Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer
Ching-Yi Chen1,2, How-Wen Ko3, Po-Wei Hu4
1Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Purpose:
In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group.
Patients And Methods:
This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes.
Results:
Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments.
Conclusion:
In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.
Insights
Small-cell lung cancer (SCLC) transformation in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs) requires further study. Combination therapies showed improved disease control but no overall survival benefit.
Area of Science:
- Oncology
- Translational Research
- Cancer Therapeutics
Background:
- Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs) can develop transformation to small-cell lung cancer (SCLC).
- This transformation is associated with poor prognoses, and optimal treatment strategies remain unclear.
Purpose of the Study:
- To investigate clinical factors and treatments associated with outcomes in patients with SCLC transformation post-EGFR-TKI therapy.
- To identify potential therapeutic approaches for this challenging clinical scenario.
Main Methods:
- Retrospective multicenter study analyzing 27 patients with SCLC transformation after advanced NSCLC EGFR-TKI treatment.
- Evaluation of clinical characteristics, first-line EGFR-TKI treatments, and subsequent regimens including chemotherapy (CT), CT/EGFR-TKI, and CT/immunotherapy.
Main Results:
- Median progression-free survival (PFS) on first-line EGFR-TKI was 16.1 months, and on subsequent SCLC treatment was 6.4 months. Overall survival (OS) was 39.5 months.
- Subsequent treatment regimens included CT (44%), CT/EGFR-TKI (37%), and CT/immunotherapy (19%).
- Disease control rates (DCRs) were 41.7% for CT, 88.9% for CT/TKI, and 100% for CT/immunotherapy. Trends towards improved overall response rate (ORR) and PFS were observed with combination therapies, but without statistical significance or OS benefit.
Conclusions:
- Adding immunotherapy and EGFR-TKI to chemotherapy in SCLC transformation post-EGFR-TKI therapy improved DCR and showed trends in ORR and PFS.
- No significant overall survival benefit was observed with combination therapies compared to traditional chemotherapy.
- Further prospective studies are needed to validate these findings and explore varied therapeutic approaches for SCLC transformation.
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