e18030 Background: Reversible tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) significantly increase survival for patients with previously treated advanced non-small cell lung cancer (NSCLC). Some studies have shown that most of responders to TKIs failed due to the appearance of new lesions without progression of the pre-existing target lesions. Methods: We retrospectively reviewed patients with advanced NSCLC diagnosed from 2005 to 2010 at two different hospitals in Catalonia (Spain) to identify those treated with TKIs. Patients with a clinical objective benefit as defined by Jackman were included. We analyzed both the clinical features of patients and their failure pattern. Results: There were 34 patients, 14 were women, with a median age of 64 years (range: 38 -81 years). Twenty-seven cases were adenocarcinoma while only 3 were squamous cell carcinoma. Eleven patients had never smoked. Previously to TKI, all patients received at least one line of chemotherapy except nine patients who received TKI as first-line treatment. Median time to progression after initiation of TKI was 8.7 months (1.9 - 38.9 months). Radiological TKI response was CR/PR/SD: 1/15/17 (1 not available). Rash and diarrhea were the most common toxic effects. No grade 3 or 4 toxicities were observed. TKI was discontinued in all patients after disease progression; 12 patients were unable to receive further therapy due to symptomatic deterioration. In 19 patients, PD was due to the appearance of new lesions and not to progression of the pre-existing lesions. Results of mutations of EGFR were available in 7 patients (ratio of mutant/wild status was 5/2). In all patients with known EGFR mutation, only new lesions leaded to progression. Conclusions: In spite of our series’ heterogeneity, results are consistent with previous data and suggest that a wide range of patients can benefit from TKIs. Furthermore, more than half of progressions were due to new lesions. Patients with known EGFR mutation strictly followed this failure pattern, though larger studies in EGFR mutated patients are needed to assess both failure patterns and benefits of continuing TKIs after progression when pre-existing lesions are stable.
PD-L1 confers resistance to EGFR mutation-independent tyrosine kinase inhibitors in non-small cell lung cancer via upregulation of YAP1 expression
