Author of

• 36512

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  P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36538

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    P84.17 - Impacts of Different EML4-ALK Variants on the Efficacy of ALK Inhibitors in ALK Positive NSCLC——A Real-World Study in China. (ID 1762)

    00:00 - 00:00  |  Presenting Author(s): Zihua Zou
    • Abstract

    Introduction
    

    Previous studies indicated that ALK fusion variants were associated with the efficacy of ALK inhibitors in ALK+ NSCLC. However, these results were still controversial. Besides, there is limited data in China that demonstrated the efficacy of ALK inhibitors in different ALK variants. We aimed to investigate the impacts of different EML4-ALK variants and ALK fusion partners on the efficacy of ALK inhibitors in the Real-world study.

    Methods
    

    We conducted a single center retrospective analysis on 33 ALK-positive NSCLC patients with detailed medical records including next-generation sequencing (NGS) results between January 2016 and February 2020. Data were collected and analyzed for overall response rate (ORR) and progression-free survival (PFS) in ALK inhibitors treated patients with different EML4-ALK variants or ALK fusion partners.

    Results
    

    Among the 33 patients with NGS results, 18 patients were treated with Crizotinib as initial ALK inhibitors therapy (17 patients received Crizotinib as first-line treatment), 15 patients received Alectinib as first-line treatment. The most common partner is EML4, forming the variant 1 (v1, E13:A20, 33.3%), variant 2 (v2, E20:A20, 12.1%), and variant 3 (v3, E6:A20, 27.3%).The percentage of rare EML4-ALK variants and non EML4-ALK variants were 12.1% and 15.1%, respectively. Our analysis showed that no significant difference of ORR was observed between patients with EML4-ALK and those with non EML4 partners (72% vs 80%,p=0.64). Also, patients with different EML4-ALK variants presented similar ORR to initial ALK inhibitors treatment both in Crizotinib and Alectinib group (Crizotinib: v1 80%, v2 66.6%, v3 66.6%, Alectinib: v1 75%, v2 100%, v3 75%). However, we found that patients with v3 appeared to have unfavorable median PFS compared with patients with non-v 3(9.2m vs 13.5m, p=0.018) in Crizotinib group, but not in other EML4 variants subgroups. At the last follow up, PFS was immature in Alectinib group, only two patients experienced disease progression with PFS shorter than 6 months, one of them carried variant 3, the other carried HIP1-ALK coupling with EGFR amplification and high PD-L1 expression.

    Conclusion
    

    Our results indicated that patients with EML4-ALK variant 3 might have unfavorable PFS with first-line Crizotinib therapy. We expected further results to explore whether Alectinib could improve this subgroup outcome.

    	Crizotinib	Alectinib
    variant1	7	4
    variant2	3	1
    variant3	5	4
    rare variants	2	2
    non-EML4 partners	1	4