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Updated: Jul 18, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
How to Treat EGFR-Mutated Non-Small Cell Lung Cancer
Neel Belani1, Katherine Liang2, Michael Fradley3
1Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Abstract:
•Mutations in the EGFR gene are observed in about 15% of NSCLC adenocarcinomas in the United States and are not associated with smoking. There are numerous EGFR mutations, with the most common being exon 19 deletions and the point mutation L858R in exon 21.•Osimertinib, an oral TKI, is used as the initial therapy for metastatic NSCLC harboring exon 19 deletion and exon 21 L858R mutation. Common side effects include acneiform rash, diarrhea, and paronychia. Osimertinib has also been associated with cardiomyopathy (∼1.4%-2.4%) and prolongation of the QT interval (2.7%).•In our experience, osimertinib-induced cardiomyopathy can be managed with the cessation of osimertinib and the initiation of guideline-directed therapy. Given that osimertinib is often the best available therapy, rechallenging with osimertinib often favors benefit over risk. Safe rechallenge with osimertinib is demonstrated in this case.
Insights
Osimertinib is a key treatment for EGFR-mutated NSCLC. This study shows that osimertinib-induced cardiomyopathy can be safely managed, allowing patients to benefit from rechallenge therapy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Epidermal Growth Factor Receptor (EGFR) mutations are common in non-small cell lung cancer (NSCLC), particularly adenocarcinomas.
- Osimertinib is a first-line targeted therapy for metastatic NSCLC with specific EGFR mutations (exon 19 deletions, exon 21 L858R).
- While effective, Osimertinib can cause side effects like rash, diarrhea, and serious cardiac issues including cardiomyopathy and QT interval prolongation.
Purpose of the Study:
- To evaluate the management and outcomes of Osimertinib-induced cardiomyopathy.
- To assess the safety and efficacy of rechallenging patients with Osimertinib after managing cardiac side effects.
Main Methods:
- Retrospective case review.
- Clinical management of Osimertinib-induced cardiomyopathy.
- Monitoring of patient outcomes during Osimertinib rechallenge.
Main Results:
- Osimertinib-induced cardiomyopathy was successfully managed by drug cessation and guideline-directed medical therapy.
- Patients who were rechallenged with Osimertinib demonstrated that the benefits outweighed the risks.
- The case series indicates that safe rechallenge with Osimertinib is feasible.
Conclusions:
- Osimertinib-induced cardiomyopathy is a manageable side effect in NSCLC patients.
- Rechallenging with Osimertinib after managing cardiac toxicity can be a safe and beneficial therapeutic strategy.
- This approach allows continued treatment with an effective therapy when Osimertinib is the optimal choice.
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