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Chemotherapy outcomes in EGFR-TKI resistant patients with common and uncommon EGFR mutation: An exploratory
Chien-Yu Lin1, Chia-Hao Hu1, Chia-Fu Hsu2
1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Background:
Some prospective studies have shown that second-generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second-line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients.
Methods:
Patients with EGFR-mutated advanced-stage NSCLC who received first-line EGFR-TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second-line chemotherapy were enrolled. We compared progression-free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan-Meier and log-rank tests.
Results:
In total, 209 (54.8%) patients had a negative T790M mutation test and received second-line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS.
Conclusion:
This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.
Insights
Non-small cell lung cancer (NSCLC) patients with uncommon epidermal growth factor receptor (EGFR) mutations showed poorer responses to second-line chemotherapy. This highlights an unmet need for novel treatment strategies in this patient group.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Second-generation tyrosine kinase inhibitors (TKIs) show promise for non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations.
- Limited data exists comparing second-line chemotherapy efficacy between NSCLC patients with common versus uncommon EGFR mutations.
Purpose of the Study:
- To compare treatment outcomes, specifically progression-free survival (PFS) and overall survival (OS), between NSCLC patients with common and uncommon EGFR mutations receiving second-line chemotherapy.
Main Methods:
- Retrospective review of advanced-stage NSCLC patients with EGFR mutations who received first-line EGFR-TKIs.
- Inclusion criteria: negative T790M test at progression and receipt of second-line chemotherapy.
- Kaplan-Meier and log-rank tests were used to compare PFS and OS between common and uncommon EGFR mutation groups.
Main Results:
- Of 209 patients receiving second-line chemotherapy, 192 (91.8%) had common EGFR mutations and 17 (8.2%) had uncommon mutations.
- Patients with common EGFR mutations demonstrated significantly longer PFS (4.57 months) compared to those with uncommon mutations (2.57 months; p=0.031).
- Uncommon EGFR mutation status was identified as an independent negative prognostic factor for PFS.
Conclusions:
- Patients with uncommon EGFR mutations exhibit inferior chemotherapy responses and reduced survival compared to those with common EGFR mutations.
- There is a critical unmet need for the development of novel therapeutic strategies for NSCLC patients with uncommon EGFR mutations.
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