Abstract 57P
Background
The resistance mechanisms to EGFR-TKIs are inevitable and heterogeneous. Secondary T790M mutation was the most frequent acquired resistance mechanism to early-generation EGFR-TKIs and osimertinib was the standard second-line therapy. Driver gene alterations like ALK and MET were increasingly observed in resistance mechanisms. Additionally, driver gene resistance overlaps with EGFR T790M accounted for 4%-8% in resistant patients. However, no good consensus was formulated.
Methods
We searched the lung cancer database of the Second Xiangya Hospital and screened for EGFR-mutant NSCLC patients who developed secondary T790M positive after early-generation EGFR-TKI. Further, Patients who had acquired T790M cooperating with driver gene resistance were included. Meanwhile, extensive literature reviews in PubMed were conducted. The efficacy and prognosis were evaluated based on the RECIST v1.1.
Results
216 EGFR-mutant NSCLC patients who received early-generation EGFR-TKI were identified in the database and 105 patients had disease progression. 57.1% (65/105) patients developed into secondary EGFR T790M and 61.5% (40/65) patients were identified by the next-generation sequencing. Two (2.0%) patients cooperated with MET amplification and ALK fusion. One patient had acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and was shortly resistant to osimertinib with MET amplification. The other patient developed to acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after 4-month osimertinib treatment. Five published cases of co-existence of EGFR T790M and HER2 amplification or KRAS G12X were identified. The presented 7 cases showed median progression-free survival (PFS) of 3 months and did not benefit from osimertinib monotherapy.
Conclusions
Patients with concurrent alterations of EGFR T790M and driver gene resistance had poor outcomes from osimertinib. Additionally, subsequent new bypass activations were possible resistance mechanisms to second-line osimertinib. The T790M accompanying diver gene resistance will be a new subtype after EGFR-TKIs progression and needs effective treatment options.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.