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Third-Generation EGFR-TKIs in T790M-Negative NSCLC After First/Second-Generation EGFR-TKI Failure: A Retrospective
Zhen Cheng1,2, Jiali Dong1, Huihao Lu1
1Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Purpose:
In non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), only half develop the T790M mutation and thus qualify for the treatment using third-generation EGFR-TKIs. For T790M-negative patients, chemotherapy is the recommended second-line treatment. We compared the efficacy between third-generation EGFR-TKIs and chemotherapy with or without first/second-generation EGFR-TKIs in T790M-negative patients.
Patients:
This study included T790M-negative patients with EGFR-mutated advanced NSCLC and progressing after first-line treatment with first- or second-generation EGFR-TKIs. Data on clinical characteristics, disease features, and survival were collected, including general conditions, medical history, imaging, histology, and molecular profiling.
Results:
Of 82 patients progressing after first- or second-generation EGFR-TKIs without acquiring T790M, 45 received third-generation EGFR-TKIs and 37 received chemotherapy and/or first/second-generation EGFR-TKIs. We found that third-generation EGFR-TKIs led to significantly longer median progression-free survival (mPFS) than other treatments [10.20 months vs. 5.70 months, p = 0.017]. Subgroup analyses indicated that third-generation EGFR-TKIs had similar mPFS to the chemotherapy group but were significantly superior to first/second-generation EGFR-TKIs with or without chemotherapy (10.20 months vs. 4.80 months, p < 0.001; 10.20 months vs. 3.30 months, p = 0.004). The median overall survival (mOS) for patients treated with third-generation EGFR-TKIs and with non-third-generation therapy was 39.80 months (95% CI 23.14 to 56.46) and 32.40 months (95% CI 18.71 to 46.09), p = 0.408, respectively.
Conclusions:
Third-generation EGFR-TKIs significantly improved mPFS in T790M-negative patients with EGFR-mutated advanced NSCLC and resistant to first-line treatment with first- or second-generation EGFR-TKIs.
Trial Registration:
ChiCTR2500096109.
Insights
Third-generation EGFR-TKIs significantly improve progression-free survival in T790M-negative non-small cell lung cancer patients resistant to earlier EGFR-TKIs. This offers a better treatment option for this patient group.
Area of Science:
- Oncology
- Pharmacology
- Medical Genetics
Background:
- Non-small cell lung cancer (NSCLC) treatment resistance to first- and second-generation EGFR-TKIs poses a clinical challenge.
- Only a subset of resistant NSCLC patients develop the T790M mutation, limiting eligibility for third-generation EGFR-TKIs.
- Chemotherapy is the standard second-line treatment for T790M-negative NSCLC patients.
Purpose of the Study:
- To compare the efficacy of third-generation EGFR-TKIs versus chemotherapy in T790M-negative advanced NSCLC patients.
- To evaluate treatment outcomes for patients resistant to first- or second-generation EGFR-TKIs but lacking the T790M mutation.
Main Methods:
- Retrospective analysis of 82 T790M-negative advanced NSCLC patients progressing after first- or second-generation EGFR-TKIs.
- Patients received either third-generation EGFR-TKIs (n=45) or chemotherapy and/or earlier-generation EGFR-TKIs (n=37).
- Collected data included clinical characteristics, disease features, and survival outcomes.
Main Results:
- Third-generation EGFR-TKIs demonstrated significantly longer median progression-free survival (mPFS) at 10.20 months compared to other treatments (5.70 months, p=0.017).
- Subgroup analysis showed third-generation EGFR-TKIs were superior to first/second-generation EGFR-TKIs with or without chemotherapy (p<0.001 and p=0.004).
- Median overall survival (mOS) was 39.80 months for third-generation EGFR-TKIs versus 32.40 months for non-third-generation therapy (p=0.408).
Conclusions:
- Third-generation EGFR-TKIs significantly improve mPFS in T790M-negative advanced NSCLC patients resistant to prior EGFR-TKIs.
- This finding supports the use of third-generation EGFR-TKIs as a viable and effective treatment option for this specific patient population.
- Further research may explore optimal sequencing and combination strategies.
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