This study enrolled 63 consecutive patients with advanced EGFR-mutant NSCLC and good performance status (PS) and who underwent first-line EGFR-TKI therapy or standard cytotoxic chemotherapy and then had progressive disease, from 2007 to 2011.
In the current era of targeted therapies, it has become clear that different patterns of progressive disease are observed with TKI treatment in EGFR-mutated NSCLC patients, with potential consequences for therapeutic decision-making.
Treatment outcomes were assessed via progression-free survival (PFS) times (PFS-1: time to PD after EGFR-TKI therapy; PFS-2: time to further PD after arterial infusion chemotherapy with EGFR-TKI therapy), the occurrence of treatment-related AEs, and patient responses to the QLQ-LC13 quality-of-life questionnaire.
Only one sample showed MMNG HOS Transforming gene (MET) amplification (the patient had progressive disease), whereas 59% (13 of 22) and 47% (14 of 30) had high levels of expression of epidermal growth factor receptor and mesenchymal-epithelial transition factor on the basis of H-scores, respectively.
In this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions.
Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding concordance of 79%, with a shorter time interval between tissue and blood collection associated with increased concordance (P = 0.038). ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy, and for whom tissue sequencing was not possible.
Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease.
Osimertinib was approved by the US Food & Drug Administration in November 2015 for patients whose tumors exhibited T790M mutation and for those with progressive disease on other EGFR TKIs.
He developed progressive disease in liver 4 months later, and the biopsy of liver metastases showed neuroendocrine carcinoma maintained the same EGFR mutation.
In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy.
Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease.
However, the levels of the EGFR exon 19 deletion driver mutation and the T790M resistance mutation in the circulating tumor DNA continued to rise and the patient died from progressive disease 6 weeks after commencement of combination therapy.
Total duration of EGFR-TKI treatment before rebiopsy, TKI-free interval, EGFR-TKI treatment history immediately before rebiopsy, continuation of initial EGFR-TKI beyond progressive disease, progression-free survival after initial TKI treatment, and rebiopsy site (other than fluid samples) significantly influenced T790M status.
In a subset of patients, we further showed that reappearance of EGFR mutations could be detected in plasma up to 5 months ahead of progressive disease (PD), suggesting an early detection of drug resistance.
We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with <i>EGFR</i>-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI.
Presented here is a case of stage IV NSCLC harboring an uncommon EGFR exon 20 insertion mutation that was maintained at minimal progressive disease for 54 months, with 36 months on the second-generation TKI afatinib.