EGFRT790M was identified from plasma DNA in 54% (15 of 28) of patients with prior clinical response to gefitinib/erlotinib, 29% (4 of 14) with prior stable disease, and in 0% (0 of 12) that had primary progressive disease or were untreated with gefitinib/erlotinib.
Five of the 13 patients with <i>EGFR</i> mutations were treated with EGFR-TKIs, two of whom manifested a partial response, two stable disease, and one progressive disease.
One of seven patients who experienced partial response had EGFR mutations only in the metastasis, and two of seven patients who experienced progressive disease carried wild-type EGFR only in the metastasis.
Patients with EGFR-activating mutations (del19 and L858R) that progressed using first-line gefitinib treatment were enrolled and treated with gefitinib beyond PD plus pemetrexed 500 mg/m<sup>2</sup> q3w.
The EGFR mutations were seen significantly more frequently in patients with a partial response than in patients with stable disease or progressive disease (P = 0.046, Fisher's exact test).
TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n = 59) and those with wild-type EGFR (n = 20).
Direct sequencing revealed wild-type EGFR, whereas PNA clamping revealed mutant EGFR, in one of five patients who exhibited progressive disease in response to EGFR tyrosine kinase inhibitor; the cell block of this patient contained a high proportion of tumor cells.
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.
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.
Awareness of this phenomenon with epidermal growth factor receptor tyrosine kinase inhibitors is important for physicians treating patients with NSCLC, so that it is not misinterpreted as progressive disease resulting in premature cessation of effective therapy.
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.
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.
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.
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.
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.
EGFR mutations (seen in 15 of 89 patients) were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease.
<b>Methods:</b> Patients with advanced NSCLC, known <i>EGFR</i> mutation and progressive disease on an EGFR TKI immediately prior to enrollment without intervening therapy were enrolled.
Among 26 patients who had received EGFR-TKIs, the mean EGFR mutation content was higher in patients showing partial response (86.1%) or stable disease (48.7%) compared with patients experiencing progressive disease (6.0%) (P = 0.001).