410P - Frequency and spectrum of primary resistance mechanism in Chinese ALK+ non-small cell lung cancer patients progressing on crizotinib: A multicenter study

Background

Anaplastic lymphoma kinase (ALK) have been recognized as the most important predictor of response to crizotinib. However, 20-30% of patients harboring ALK fusion non-small-cell lung cancer patients show a poor response requiring investigation for underlying mechanisms.

Methods

We screened 3207 patients with NSCLC for ALK fusion. Among them, 92 patients received crizotinib treatment,and a total of 81 patients with stage IIIb-IV ALK+NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring resistance to crizotinib, including 43 formalin-fixed paraffin-embedded (FFPE) samples, 25 serum samples and 24 serous effusions. We used targeted NGS to detect genes status of patients.

Results

Among 92 patients treated with crizotinib, 76.09% (70/92) developed acquired resistance, and 11.96% (11/92) had primary resistance. Using the specimens at the baseline, there were 2 (18.18%) patients with BCL2L11 loss (BIM deletion polymorphism), 1 (9.09%) patient with PTEN mutation, 1 (9.09%) patient with PIK3CA mutation, 1 (9.09%) patient with CCND1 mutation, 1 (9.09%) patient with SMARCA4 mutation, 1 (9.09%) patient with CMTR1-ALK, 1 (9.09%) patient with EML4-ALK fusion (non A20), and 3 (27.27%) patients with unknown status.

Conclusions

BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), SMARCA4 mutations or EML4-ALK fusion (non A20) might contribute to molecular mechanisms of primary resistance to crizotinib in ALK+NSCLC.Further investigations are warranted to overcome these primary resistance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Chun-wei Xu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.