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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
Non-small-cell lung cancer with epidermal growth factor receptor L861Q-L833F compound mutation benefits from both
Yao Zhang1, Ji-Qiao Shen1, Lin Shao2
1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been adopted as the standard of care for non-small cell lung cancer (NSCLC) patients harboring EGFR sensitizing mutations. Besides the two common mutations exon 19 deletion and L858R, which together comprise approximately 85% of EGFR mutations in NSCLC, rare EGFR mutations also exist, including point mutations, deletions, and insertions spanning EGFR exons 18-25. However, the responsiveness of uncommon EGFR mutations to EGFR TKIs remains elusive and attracts increasing interest.
Case Summary:
Herein, we report a 55-year-old male patient with stage IV NSCLC harboring a rare EGFR L833F-L861Q compound mutation in cis. The patient achieved a partial response to first-line treatment with afatinib and a progression-free survival of 10 mo. After afatinib failure, the patient received multiple line treatments with chemotherapy. Upon disease progression, the heavily pretreated patient was treated with osimertinib and bevacizumab, and both lung lesion and brain metastases were stable for more than 3 mo. He had an overall survival of 25 mo.
Conclusion:
Our case revealed that both afatinib and the osimertinib + bevacizumab combination demonstrated clinical efficacy in NSCLC harboring an EGFR L833F-L861Q compound mutation. The results provide more therapeutic options for patients with rare compound mutations.
Insights
This case study shows afatinib and osimertinib plus bevacizumab are effective treatments for non-small cell lung cancer (NSCLC) with rare EGFR L833F-L861Q mutations. These findings offer new therapeutic options for patients with uncommon EGFR mutations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard for non-small cell lung cancer (NSCLC) with sensitizing mutations.
- Common EGFR mutations (exon 19 deletion, L858R) account for ~85% of cases.
- Rare EGFR mutations, including point mutations, deletions, and insertions in exons 18-25, have unclear responses to EGFR TKIs.
Observation:
- A 55-year-old male with stage IV NSCLC presented with a rare EGFR L833F-L861Q compound mutation in cis.
- Initial treatment with afatinib resulted in a partial response and 10 months of progression-free survival.
- Following afatinib failure and chemotherapy, the patient received osimertinib plus bevacizumab, achieving stable disease for over 3 months.
Findings:
- Afatinib demonstrated clinical efficacy in NSCLC with the rare EGFR L833F-L861Q compound mutation.
- The combination of osimertinib and bevacizumab also showed efficacy in this patient with advanced NSCLC.
- The patient achieved an overall survival of 25 months.
Implications:
- This case highlights the potential efficacy of afatinib and osimertinib plus bevacizumab for NSCLC patients with rare EGFR compound mutations.
- These findings expand therapeutic options for a subset of NSCLC patients with uncommon genetic alterations.
- Further research into the treatment of rare EGFR mutations is warranted.
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