Abstract 966
Background
Crizotinib have greatly improved the prognosis of ROS1+ lung adenocarcinoma. However, approximately 5% to 10% of patients with ROS1+ non-small-cell lung cancer (NSCLC) have primary resistance to crizotinib treatment. The underlying mechanism is unknown.
Methods
We screened 2617 patients with NSCLC for ROS1 fusion. Among them, 23 patients received crizotinib treatment, and a total of 20 patients with stage IIIb-IV ROS1+ NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring resistance to crizotinib, in including 4 formalin-fixed paraffin-embedded (FFPE) samples, 13 serum samples and 3 serous effusions. We used targeted NGS to detect genes status of patients.
Results
Among 23 patients treated with crizotinib, 73.9% (17/23) developed acquired resistance, and 13.04% (3/23) had primary resistance. Using the specimens at the baseline, there was 1 (33.3%) patient with BCL2L11 loss (BIM deletion polymorphism), 1 (33.3%) patient with PTEN mutation, and 1 (33.3%) patient with KIT mutation. Median PFS was significantly shorter in patients with primary resistance than those with acquired resistance (2.3 vs. 14.5 months, P < 0.001).
Conclusions
BCL2L11 loss, PTEN mutation, and KIT mutation might contribute to molecular mechanisms of primary resistance to crizotinib in ROS1+ NSCLC. Further investigations are warranted to overcome these primary resistances.
Clinical trial identification
Legal entity responsible for the study
Quxia Zhang.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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