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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Real-World Evidence for First-Line afatinib in Advanced Non-Small Cell Lung Cancer With Uncommon Epidermal Growth
Thanh Ha Vu1,2, Hoa Thai Thi Nguyen2, To Van Ta3
1Department of Oncology, Hanoi Medical University, Hanoi, Viet Nam.
Abstract:
IntroductionRare epidermal growth factor receptor (EGFR) mutations other than G719X, S768I, and L861Q are infrequently represented in clinical trials. The efficacy of tyrosine kinase inhibitors (TKIs) against these uncommon variants, either alone or in combination with common mutations, remains limited.MethodsWe retrospectively analyzed patients with advanced-stage non-small cell lung cancer (NSCLC) harboring non-major uncommon EGFR mutations who received first-line afatinib between January 2018 and October 2024. Patients with only TKI-sensitive mutations (Del19, L858 R, G719X, S768I, and L861Q) and without additional rare variants were excluded. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoint was the duration of response (DOR).ResultsAmong the 44 patients, 36.4% had solitary non-major uncommon mutations. The overall ORR and the disease control rates were 65.9% and 86.4%, respectively. The ORR by subgroup was 75.0% for patients with non-major uncommon mutations plus EGFR-TKI-sensitive mutations, and 55.0% for patients with dual or solitary uncommon mutations. At a median follow-up time of 21.9 months, the median PFS was 11.5 months (95% CI: 7.5-22.6). Patients with non-major uncommon mutations co-occurring with TKI-sensitive mutations had a longer median PFS (17.7 months; 95% CI: 13.6-NR) than those harboring non-major mutations alone (either single or dual) (9.1 months; 95% CI: 4.6-NR), P = 0.04. The median duration of response was 16.1 months (95% CI: 10.3-NR) with a median follow-up time of 16.8 months.ConclusionAfatinib demonstrated encouraging efficacy in NSCLC patients with nonmajor uncommon EGFR mutations other than G719X, S768I, and L861Q, regardless of whether the mutations were solitary or compound. Comprehensive EGFR mutation profiling is crucial for identifying uncommon EGFR mutation patients likely to benefit significantly from afatinib.
Insights
Afatinib shows promising efficacy in non-small cell lung cancer (NSCLC) patients with rare epidermal growth factor receptor (EGFR) mutations. Comprehensive EGFR profiling helps identify patients who can benefit from afatinib treatment.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Rare epidermal growth factor receptor (EGFR) mutations are underrepresented in clinical trials for non-small cell lung cancer (NSCLC).
- The efficacy of tyrosine kinase inhibitors (TKIs) against these uncommon EGFR variants, alone or with common mutations, is not well-established.
- Limited data exists on the effectiveness of afatinib in NSCLC patients with non-major uncommon EGFR mutations.
Purpose of the Study:
- To evaluate the efficacy of first-line afatinib in advanced-stage NSCLC patients with non-major uncommon EGFR mutations.
- To determine the objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) in this patient population.
- To compare outcomes between patients with solitary/dual uncommon mutations versus those with uncommon mutations co-occurring with TKI-sensitive mutations.
Main Methods:
- Retrospective analysis of 44 advanced-stage NSCLC patients treated with first-line afatinib.
- Inclusion criteria: patients with non-major uncommon EGFR mutations, excluding those with only TKI-sensitive mutations without additional rare variants.
- Primary endpoints: ORR and PFS. Secondary endpoint: DOR.
Main Results:
- The overall ORR was 65.9%, with a disease control rate of 86.4%.
- ORR was higher in patients with non-major uncommon mutations plus EGFR-TKI-sensitive mutations (75.0%) compared to those with dual or solitary uncommon mutations (55.0%).
- Median PFS was 11.5 months; patients with co-occurring TKI-sensitive mutations had significantly longer PFS (17.7 months) than those with only uncommon mutations (9.1 months, P=0.04). Median DOR was 16.1 months.
Conclusions:
- Afatinib demonstrates encouraging efficacy in NSCLC patients with non-major uncommon EGFR mutations (excluding G719X, S768I, L861Q), whether solitary or compound.
- Comprehensive EGFR mutation profiling is crucial for identifying NSCLC patients who may significantly benefit from afatinib.
- Afatinib represents a viable treatment option for NSCLC patients harboring specific uncommon EGFR mutations.
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