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Are all ALK variants created equal? Clinicopathologic features and outcomes: a propensity-matched study

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Abstract

Anaplastic lymphoma kinase (ALK) rearranged NSCLC comprises a molecularly distinct subgroup occurring in 10% cases. Various EML4–ALK and non EML4 variants are known to occur which can be detected only on NGS and show differential TKI responses. 113 ALK-IHC positive cases were subjected to a custom panel-based NGS for detection of ALK variants. Clinicopathologic features and outcomes were studied and propensity-matched analysis was done. The median age of the overall cohort was 53 years. 91 (80.5%) cases were NGS positive, the most common being EML4–ALK (90, 98.9%) cases. The most common EML4 variant was Variant 1 (40, 35%) cases, Variant 3 (28, 25%) cases, and Variant 2 (17, 15%) cases. One novel EML4–ALK variant was also encountered which was found to be intrinsically resistant to crizotinib. On pre-weight-adjusted comparison, Variant 1 group had a higher occurrence of brain and extrathoracic metastases. The median OS was 44 months for the entire cohort. 49 patients received crizotinib as first-line TKI. Among these, the median OS for Variant 2 was not reached; it was 38 months and 24 months for Variant 1 and Variant 3, respectively. The median PFS for crizotinib treated patients was 8.3 months (Variant 2: 11 months, Variant 1: 8 months, and Variant 3: 9 months). On propensity-matched analyses, there was no difference in OS and PFS between Variant 1 and Variant 3, with higher HR for Variant 3. We present a large data set evaluating clinical and outcome differences between ALK variants. The unique standpoint of this study involves the propensity-weighted model to account for differences among the groups, with no prognostic differences between Variant 1 and Variant 3, which is distinct from literature.

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Acknowledgements

Pfizer Educational Grant : Pfizer Global Grants: Educational grant number: WI244144. We acknowledge the efforts of staff nurses, research coordinators, and doctors of medical oncology department of RGCI.

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Authors and Affiliations

  1. Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5 Rohini, Sir Chhotu Ram Marg, New Delhi, 110085, India

    Ullas Batra, Mansi Sharma & Parveen Jain

  2. Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

    Shrinidhi Nathany

  3. Department of Laboratory Services, Molecular Diagnostics and Transfusion Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

    Anurag Mehta

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  1. Ullas Batra
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  2. Mansi Sharma
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  6. Anurag Mehta
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Correspondence to Ullas Batra.

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Batra, U., Sharma, M., Nathany, S. et al. Are all ALK variants created equal? Clinicopathologic features and outcomes: a propensity-matched study. Int J Clin Oncol 26, 1221–1228 (2021). https://doi.org/10.1007/s10147-021-01916-w

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  • DOI: https://doi.org/10.1007/s10147-021-01916-w

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