Abstract 69P
Background
Scholars had made much progress on the investigation about tumor invasiveness, response to ALK inhibitors and resistance mechanism in different ALK variants, however, these studies had reached inconsistent conclusions. We conducted this research with relatively larger sample size to make more comprehensive analysis.
Methods
Medical records of ALK+ NSCLC patients with stage III/IV or with recurrence after the surgery who received first-line alectinib or crizotinib were retrospectively collected in our center. Information of ALK variants was confirmed through the detection of patient’s samples either at the time of diagnosis or progression. We analyzed the tumor invasiveness, response to ALK inhibitors, progression pattern and resistance mechanism in different ALK variants. Shorter EML4 variants included EML4 fusions up to exon 6 and longer EML4 variants contained EML4 fusions at least exon 13.
Results
120 patients were included in our research(alectinib cohort: n=61, crizotinib cohort: n=59). Shorter EML4-variants were identified in 42 patients while 59 patients carried longer EML4-variants. The extent of tumor dissemination before the initiation of targeted therapy was similar between shorter and longer variants. In alectinib cohort, shorter forms presented numerically lower response rate than their counterparts(75% vs 95.5%, p=0.141), meanwhile, patients with shorter variants experienced significantly unfavorable PFS(NE vs NE, p=0.0453, HR=3.24(95%CI: 0.94 to 11.2)), however, this was not the case in patients treated with first-line crizotinib(ORR: 85% vs 91.7%, p=0.828, PFS: 11.0m vs 12.9m, p=0.349,HR=1.3(95%CI: 0.72 to 2.3)). Higher frequency of ALK secondary mutation(64.7% vs 38.5%, p=0.269)was reported in shorter forms, additionally, for patients who developed ALK secondary mutation, G1202R was much more common in shorter EML4 variants(90.9% vs 0%,p=0.001).
Conclusions
Our study indicated different response to ALK inhibitors and resistance mechanism between shorter and longer EML4-variants, therefore, more pertinent treatment strategy was in need of further exploration for different ALK variants.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.