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Lung Cancer Treatments and Mutations / Lung Cancer Diagnosis and Treatment · Journal article
Frontiers in Oncology · September 9, 2026
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This is a single case report of a 62-year-old male with EGFR L858R-mutant lung adenocarcinoma who developed sequential bypass resistance mutations (MET amplification, BRAF V600E, RET fusion) during aumolertinib treatment, tracked by serial NGS. The clinical course—11 months PFS on aumolertinib plus savolitinib, followed by transient response to selpercatinib plus chemotherapy—is presented as an illustration of dynamic clonal evolution under selective pressure, with speculation that TP53 accumulation may indicate poor prognosis, but the case does not establish causation or provide evidence for therapeutic utility.
Single case report with serial molecular profiling. 62-year-old male with stage IIB poorly differentiated lung adenocarcinoma harbouring EGFR L858R mutation; treated with adjuvant aumolertinib after surgical resection.. Intervention: Serial NGS monitoring and genotype-guided therapy: aumolertinib; aumolertinib plus savolitinib; selpercatinib plus chemotherapy.. n = 1.
Sequential bypass resistance evolution: initial MET amplification, followed by BRAF V600E and RET fusion, then MET re-emergence with rising TP53 VAF 11-month progression-free survival with aumolertinib plus savolitinib Subsequent selpercatinib plus chemotherapy provided only transient disease stabilization
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This case illustrates a mechanism of sequential bypass resistance evolution in EGFR-mutant NSCLC under selective TKI pressure and supports the rationale for serial molecular profiling to guide treatment decisions; however, the single-patient nature precludes any recommendation for clinical practice change.
A single case report with serial molecular profiling showing clonal evolution under treatment; descriptive and hypothesis-generating but lacking comparative data, control arm, or generalizable evidence of clinical benefit.
As stated by the source record.
Quoted from the source exactly as published.
This case illustrates a mechanism of sequential bypass resistance evolution in EGFR-mutant NSCLC under selective TKI pressure and supports the rationale for serial molecular profiling to guide treatment decisions; however, the single-patient nature precludes any recommendation for clinical practice change.
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Third-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved outcomes for patients with EGFR -mutant non-small-cell lung cancer (NSCLC). However, acquired resistance remains a critical clinical challenge.Here, we present the case of a 62-year-old male with stage IIB poorly differentiated lung adenocarcinoma harboring an EGFR L858R mutation. The patient received adjuvant aumolertinib following surgical resection. Serial sampling and dynamic next-generation sequencing (NGS) revealed a sequential bypass resistance clone evolution trajectory in this patient: initial MET amplification was followed by the detection of a BRAF V600E mutation concurrent with RET fusion, while in the terminal phase, MET amplification re-emerged alongside a progressively increasing TP53 variant allele frequency (VAF).Genotype-guided therapy adjustments yielded an 11-month progression-free survival (PFS) with aumolertinib plus savolitinib, whereas subsequent selpercatinib combined with chemotherapy provided only transient disease stabilization. Ultimately, the patient died of respiratory and circulatory failure due to progressive disease complicated by diffuse carcinomatous lymphangitis. Based on current evidence, we speculate that these bypass resistance alterations are driven by reactivation of the MAPK and PI3K/AKT signaling cascades. The progressive increase in TP53 mutant allele frequency was temporally concordant with the sequential emergence of bypass resistance mechanisms, suggesting an unfavorable prognosis. However, its utility in guiding therapeutic modifications requires further validation. This case illustrates that EGFR L858R-mutant lung adenocarcinoma can undergo stepwise clonal evolution of multiple bypass resistance mechanisms under aumolertinib selective pressure. Dynamic NGS profiling enables real-time tracking of resistant clone evolution to inform individualized treatment strategies.
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