Rebiopsy of non–small cell lung cancer patients with acquired resistance to epidermal growth factor receptor‐tyrosine kinase inhibitor

Abstract

BACKGROUND:The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence of T790M predicts a favorable prognosis and indolent progression. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation. METHODS: The study investigated 78 EGFR-mutant patients who had undergone rebiopsy after TKI failure. The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used in EGFR mutational analyses. Various patient characteristics and postprogression survivals (PPSs) after initial TKI failure were retrospectively compared in patients with and without T790M. RESULTS: The T790M mutation was identified in 4 (17%) of 24 central nervous system lesions, and in 22 (41%) of 54 other lesions (P 5.0417). No other characteristics had a statistical association with T790M prevalence. Median PPS was 31.4 months in 26 patients with T790M, and 11.4 months in 52 patients without T790M (P 5.0017). In the multivariate analysis, statistically significant factors for longer PPS included T790M-positive, good performance status, and no carcinomatous meningitis. CONCLUSIONS: The emergence of T790M in central nervous system lesions was rare, compared with other lesions. Patients with T790M after TKI failure appear to have better prognoses than those without T790M. TKI rechallenge or continuous administration beyond progression may be effective after initial TKI failure. Cancer 2013;119:4325-32.

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…This recommendation is evidence based and supported by 5 studies, 218e222 including 1 MA, 222 2 single-arm phase I nonrandomized clinical trials, 220,221 1 PCS, 219 and 1 RCS. 218 All studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 24). Refer to SDC Table 25 for a summary of findings from the studies supporting the use of EGFR T790M mutation testing when selecting patients for thirdgeneration EGFR-targeted therapy.…”

Effect of AXL on the epithelial-to-mesenchymal transition in non-small cell lung cancer

“…Therefore, downregulation of AXL expression may be considered an effective tool for lung cancer therapy (28). Alterations in AXL-associated signaling pathways have been observed in ~20% of patients with acquired resistance to EGFR-TKI (29), although it remains to be determined whether these patients would benefit from AXL inhibition. In EGFR-TKI resistance, AXL may act as a bypass to activate downstream signals associated with cell survival and growth (30).…”

Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis

“…In fact, data for the relationship between EGFR expression on the protein level and response to EGFR specific therapies is inconsistent (36). Nevertheless, an increased EGFR gene copy number has recently been proposed as a predictor of anti-EGFR targeted therapies in lung cancer patients (37). The evaluation of EGFR gene status by FISH is delicate: EGFR gene variations in tumor cells are focal and low levels of EGFR amplification are difficult to visualize.…”