Pre-TKI and post-TKI biopsies from 27 patients with an activating EGFR mutation were collected and analyzed for EGFR-T790M mutation, MET amplification, and SCLC transformation.
In this study, we report an unexpected favorable response to etoposide and cisplatin (EP) from an <i>EGFR</i>-mutant patient who developed SCLC transformation at disease progression after the administration of erlotinib with a progression-free survivalof 7.7 months.
Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression ≥50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined.
Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma.
Clinicopathologic information was analyzed and EGFR mutation results were performed in initial biopsy samples.Seven patients showed transformation from ADC to SCLC, of which 6 patients were 19 del EGFR mutation, only 1 patient is L858R mutations.
Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines.
Clinically, EGFR-positive NSCLC acquires several resistance mechanisms during EGFR-TKI treatment, such as the emergence of a secondary mutation (T790M), MET gene amplification, and transformation to small cell lung cancer.
The distinct histologic components in patients with de novo combined SCLC/NSCLC and those with adenocarcinoma exhibiting small cell transformation showed high consistency in EGFR/TP53/RB1 mutations, and expression patterns of p53 and Rb.
Overall, a secondary biopsy is important for the evaluation of genetic and histological changes and the selection of an appropriate treatment following tyrosine kinase inhibitor (TKI) resistance, and NSE may be useful for the early detection of SCLC transformation in cases that are resistant to EGFR-TKI therapy.
Small cell lung cancer (SCLC) transformation is one of the resistance mechanisms associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
We report a case of initial lung adenocarcinoma in which transformation to small cell lung carcinoma (SCLC) was observed after acquired resistance to the 3<sup>rd</sup> generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib and alternating treatment between chemotherapy and osimertinib was effective.
The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs.
The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer.
Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib.
To date, few studies have investigated whether tumor markers for SCLC correlate with the SCLC transformation in EGFR-mutant NSCLC and ALK-positive non-SCLC (NSCLC).
We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma.
For patients stable on most appropriate treatment, the mean HUSs were 0.81 and 0.82 in patients receiving EGFR and ALK tyrosine kinase inhibitors (TKIs) respectively (with similar HUSs across agents), which were higher than patients with WT NSCLC (0.78; P = .04) and SCLC receiving chemotherapy (0.72; P = .06).
Such EGFR-independent EGFR-mutant cancer cells include cells that have undergone epithelial-to-mesenchymal transition (EMT) or transformed to small cell lung cancer, which almost completely lack EGFR dependency.
Several mechanisms for this acquired resistance have been identified, including development of an EGFRT790M mutation, MET amplification, hepatocyte growth factor overexpression, loss of phosphatase and tensin homolog expression, epithelial-mesenchymal transition, and transformation to small cell lung cancer.