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Afatinib and Cetuximab in Four Patients With EGFR Exon 20 Insertion-Positive Advanced NSCLC
Bianca van Veggel1, Adrianus J de Langen1, Sayed M S Hashemi2
1Department of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Introduction:
EGFR exon 20 insertions comprise 4% to 9% of EGFR mutated NSCLC. Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses.
Methods:
Four patients with EGFR exon 20 insertion-positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250 mg/m2 to 500 mg/m2 every 2 weeks.
Results:
All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n = 4) and EGFR TKI (n = 2). Three of four patients showed a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Median progression-free survival was 5.4 months (95% confidence interval: 0.0 - 14.2 months; range 2.7 months - 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients.
Conclusions:
Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion-positive NSCLC.
Insights
Dual blockade of epidermal growth factor receptor (EGFR) using afatinib and cetuximab showed partial responses in non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertions. This combination therapy offers a potential new treatment strategy for this resistant NSCLC subtype.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- EGFR exon 20 insertions are a subset of EGFR-mutated non-small cell lung cancer (NSCLC).
- These mutations confer primary resistance to standard EGFR tyrosine kinase inhibitors (TKIs).
Purpose of the Study:
- To investigate the efficacy of dual EGFR blockade using afatinib and cetuximab in NSCLC patients with EGFR exon 20 insertions.
- To assess tumor response and progression-free survival in this patient population.
Main Methods:
- A cohort of four patients with stage IV NSCLC and EGFR exon 20 insertion mutations received afatinib and cetuximab.
- Patients had prior treatment with chemotherapy and/or EGFR TKIs.
Main Results:
- Three out of four patients achieved a partial response based on RECIST 1.1 criteria.
- Median progression-free survival was 5.4 months.
- Treatment was manageable with acceptable toxicity.
Conclusions:
- Dual EGFR blockade with afatinib and cetuximab demonstrates potential therapeutic activity in EGFR exon 20 insertion-positive NSCLC.
- This combination represents a promising strategy for a difficult-to-treat NSCLC subgroup.
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Functional groups are groups of atoms with specific chemical properties that occur within organic molecules and are sometimes denoted as “R”. Functional groups can “functionalize” a compound by enabling it to adopt different physical and chemical properties.
Types of Advanced Functional Groups
The table below summarizes some of the major functional groups in organic chemistry.