Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Abstract

BackgroundThird-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure.MethodsThis study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different first-generation EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI.ResultsOverall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progression-free survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ≥10 months following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days.ConclusionIn patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

Comparison of PNA Clamping-assisted Fluorescence Melting Curve Analysis and PNA Clamping in Detecting EGFR Mutations in Matched Tumor Tissue, Cell Block, Pleural Effusion and Blood of Lung Cancer Patients With Malignant Pleural Effusion

“…Conclusion: The diagnostic performance of PANAMutyper™ was superior to that of PNAClamp™ for the detection of EGFR mutations. It was also better at identifying lung cancer patients with malignant pleural effusion who were likely to benefit from EGFR-TKI treatment.The use of molecular agents targeting the epidermal growth factor receptor (EGFR) is important in the treatment of advanced non-small cell lung cancer (NSCLC) (1-3).Multiple prospective clinical trials have demonstrated that patients with advanced NSCLC harboring activating mutations in the EGFR gene show improved objective response rates and progression-free survival (PFS) when treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) (1,2,(4)(5)(6)(7)(8). Therefore, molecular testing for EGFR mutations has become essential for predicting whether a patient will benefit from EGFR-TKI targeted therapy (9).Previously, we compared peptide nucleic acid (PNA) clamping with direct sequencing for the detection of EGFR and K-RAS mutations.…”

“…Multiple prospective clinical trials have demonstrated that patients with advanced NSCLC harboring activating mutations in the EGFR gene show improved objective response rates and progression-free survival (PFS) when treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) (1,2,(4)(5)(6)(7)(8). Therefore, molecular testing for EGFR mutations has become essential for predicting whether a patient will benefit from EGFR-TKI targeted therapy (9).…”

Erlotinib as a salvage treatment after gefitinib failure for advanced non-small-cell lung cancer patients with brain metastasis

“…We summarized the treatment process after gefitinib resistance and the characteristics of patients suitable for continuing EGFR-TKI treatment (Figure 2). Previous studies have shown that patients who has better performance status (PS) scores, a long-term response of (longer PFS) or washout period of chemotherapy between gefitinib and erlotinib, can benefit from erlotinib after gefitinib failure [48–50] . Nowadays, with the widespread development of NGS, second biopsies to identify genetic status after gefitinib treatment make the beneficiaries of second-line erlotinib treatment found with more possibilities.…”

“…Previous studies have shown that patients who has better performance status (PS) scores, a long-term response of (longer PFS) or washout period of chemotherapy between gefitinib and erlotinib, can benefit from erlotinib after gefitinib failure. [48][49][50] Nowadays, with the widespread development of NGS, second biopsies to identify genetic status after gefitinib treatment make the beneficiaries of second-line erlotinib treatment found with more possibilities. We hanker for prospective randomized controlled trials to look for more evidence to support our inference.…”

Expression and copy number gains of the RET gene in 631 early and mid stage non‐small cell lung cancer cases

“…NSCLC has one of the highest incidences of cancer globally and causes the highest rate of cancer‐related death. During the past decades, targeted drugs, such as EGFR and ALK TKIs have been developed and have shown good therapeutic effects . Although several genetic mutations have previously been reported, no cancer genome mutation has been observed in a large proportion of NSCLC patients.…”