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Updated: Dec 21, 2025
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
[Management of a patient with a double EGFR and MET anomaly by combined treatment]
L Jénot1, I Rouquette2, J Mazieres1
1Service de pneumologie, hôpital Larrey, université Paul-Sabatier, CHU Toulouse, France.
Introduction:
Lung cancer displays molecular anomalies for which targeted therapies are the standard first line treatment. The EGFR mutation is present in 10% of cases of non-small cell lung cancer in Caucasians. MET amplification associated with an exon 19 EGFR mutation has been identified though it is usually regarded as a mechanism of resistance.
Case Report:
We report the case of a 74-year-old never-smoking woman who was diagnosed with stage IV bronchial adenocarcinoma showing both EGFR mutation and MET amplification. Initial treatment with gefitinib did not control the disease. Platinum-based chemotherapy with pemetrexed maintenance allowed a temporary response. Treatment with durvalumab for 27 months was associated with disease stability. Single agent crizotinib was associated with a slight response followed by progression. The concomitant introduction of crizotinib and gefitinib led to a spectacular and durable response with no safety issues.
Conclusions:
This case highlights the efficacy of concomitant treatment in a patient with two oncogenic drivers.
Insights
This lung cancer case study shows that combining targeted therapies for EGFR mutation and MET amplification can achieve a durable response. This approach offers new hope for patients with these specific molecular anomalies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) treatment relies on targeted therapies for molecular anomalies.
- Epidermal growth factor receptor (EGFR) mutations occur in 10% of Caucasian NSCLC patients.
- MET amplification with EGFR mutations is often a resistance mechanism.
Observation:
- A 74-year-old never-smoker with stage IV bronchial adenocarcinoma presented with both EGFR mutation and MET amplification.
- Initial gefitinib treatment failed; chemotherapy and durvalumab provided temporary control.
- Sequential crizotinib showed limited efficacy, but combination therapy with crizotinib and gefitinib yielded a significant response.
Findings:
- Concomitant crizotinib and gefitinib therapy resulted in a spectacular and durable response.
- This combination demonstrated efficacy without safety concerns in a patient with dual oncogenic drivers.
- The study challenges the view of MET amplification solely as a resistance mechanism.
Implications:
- Dual targeted therapy can be effective in NSCLC with concurrent EGFR mutations and MET amplification.
- This case suggests a potential strategy for overcoming resistance to single-agent targeted therapies.
- Further research into combination therapies for NSCLC with multiple driver mutations is warranted.
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