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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Tuesday, February 4, 2025
Treatment with EGFR tyrosine kinase inhibitors (TKIs) may be an effective management strategy in patients with non–small cell lung cancer (NSCLC) harboring BRAF class 3 mutations, according to a study published in JCO Precision Oncology. However, given the low patient population in the present study, additional studies investigating the clinical efficacy of this therapeutic approach are warranted, explained Francesco Gelsomino, MD, PhD, of IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, and colleagues.
“BRAF class 3 mutations may identify patients with NSCLC who could benefit from existing targeted therapies, paving the way for clinical trials in a population currently orphan of targeted treatments,” the investigators noted.
The study focused on two patients with advanced or metastatic NSCLC harboring BRAF class 3 mutations. Both patients had experienced treatment failure with previous therapies and were treated with erlotinib at the current institution. Cell lines were collected from these two patients to assess their clinical response to erlotinib treatment. Cell lines from KRAS-mutated and BRAF class 1– and 2–mutated NSCLC were also collected and used as controls.
After treatment with erlotinib, one patient achieved a complete response, and the other achieved a partial response to therapy. In addition, analyses performed on the cell lines revealed a reduction in EGFR activation after erlotinib treatment in the EGFR-mutated and BRAF class 3–mutated cell lines. These cell lines also had elevated baseline levels of phosphorylated EGFR. In contrast, the KRAS-mutated, BRAF class 1–mutated, and BRAF class 2–mutated lines did not show a reduction in EGFR activation. Furthermore, growth inhibition was demonstrated in the BRAF class 3–mutated and BRAF class 2–mutated cell lines after treatment with erlotinib. Moreover, an increased sensitivity to EGFR TKIs was observed in the BRAF class 3–mutated cell line compared with the KRAS-mutated and BRAF class 2–mutated cell lines.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
