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Durable response to afatinib in an advanced lung adenocarcinoma patient with an EGFR L858R/G729A compound mutation: a
Lige Wu1, Cheng Fang1, Weiqing Zhao1
1Department of Oncology, Third Affiliated Hospital of Soochow University, Changzhou, China.
Abstract:
Of the epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC), 10-15% are uncommon mutations. Most of the EGFR "major" uncommon mutations have shown responses to EGFR-tyrosine kinase inhibitors (TKIs). However, there is a lack of clinical data for other less common types of EGFR mutations and the response to EGFR-TKIs, occurring either alone or in combination with EGFR sensitizing mutations. We reported a 70-year-old Chinese man with no smoking history who was diagnosed with stage IVA lung adenocarcinoma. An exceptionally uncommon EGFR G729A mutation in EGFR exon 19 was detected concomitantly with EGFR L858R in exon 21 in tumor specimens by next generation sequencing (NGS). This patient obtained limited benefit from icotinib and the increase in symptoms of cough and chest tightness, so we decided to switch the treatment to afatinib. Our patient exhibited partial response to afatinib with progression-free survival of 10 months. Subsequently, an EGFR T790M mutation was detected in the second lung biopsy. Then, osimertinib was administered and the symptoms improved significantly and the progress-free survival was nearly 16 months. Our data suggests that patients with NSCLC who are positive for uncommon EGFR G729A mutations may benefit from treatment with afatinib.
Insights
Uncommon epidermal growth factor receptor (EGFR) G729A mutations in non-small cell lung cancer (NSCLC) may respond to afatinib. This case study highlights a patient who benefited from afatinib and subsequent osimertinib treatment.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Uncommon epidermal growth factor receptor (EGFR) mutations occur in 10-15% of non-small cell lung cancer (NSCLC) patients.
- While some uncommon EGFR mutations respond to EGFR-tyrosine kinase inhibitors (TKIs), clinical data for rarer mutations remains limited.
- Understanding the efficacy of EGFR-TKIs for uncommon mutations, alone or with sensitizing mutations, is crucial for treatment optimization.
Observation:
- A 70-year-old Chinese male with stage IVA lung adenocarcinoma, negative for smoking history, was identified with concomitant EGFR G729A (exon 19) and EGFR L858R (exon 21) mutations via next-generation sequencing.
- Initial treatment with icotinib provided limited benefit, with persistent cough and chest tightness.
- Switching to afatinib resulted in a partial response and 10 months of progression-free survival.
Findings:
- Following progression, a secondary EGFR T790M mutation was detected.
- Subsequent treatment with osimertinib led to significant symptom improvement and nearly 16 months of progression-free survival.
- The patient's response suggests that afatinib may be a viable treatment option for NSCLC patients with the uncommon EGFR G729A mutation.
Implications:
- This case report contributes valuable clinical data on the treatment of rare EGFR mutations in NSCLC.
- It suggests that afatinib could be an effective therapeutic strategy for patients harboring the EGFR G729A mutation.
- Further research into the efficacy of various EGFR-TKIs for uncommon EGFR mutations is warranted to guide personalized treatment approaches.
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