Half of the patients with disease characterized by a known ALK resistance mutation to crizotinib (32 individuals), achieved an investigator-assessed partial response to alectinib.

Median investigator-assessed progression-free survival (PFS) was shorter in the ALK-mutation subgroup compared with the subgroup without an ALK mutation (5.6 months vs 10.3 months, respectively), and the objective response rates to alectinib for the ALK mutation vs no ALK mutation subgroups were 48% and 55%, respectively, when assessed by the investigator, and were 35% and 45%, respectively, when assessed by an independent review committee.

Corresponding disease-control rates were 85% and 89% (investigator-assessed) and 83% and 85% (independent review) for those in the ALK mutation and no ALK mutation subgroups, respectively.

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Regarding the 49 patients from whom ctDNA specimens were collected following disease progression on alectinib, 16 distinct ALK mutations, including those known to be associated with alectinib resistance (eg, G1202R), were identified in 47% of patients, with no ALK mutations observed in the remaining 53%.

ALK mutations appearing during treatment with alectinib included I1171N and I1171S, G1202R, G1269A, and L1196M.

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Limitations of this analysis identified by the study authors included the absence of comparator arms from the 2 studies, as well the lack of matched tumor specimens.

In their concluding remarks, the study authors noted that “further research is needed to determine non-ALK mediated mechanisms of resistance.”

Disclosure: Some of the authors of the featured study disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.


  1. Noé J, Lovejoy A, Ou S-H I, et al. ALK mutation status before and after alectinib treatment in locally advanced or metastatjc ALK-positive NSCLC: Pooled analysis of two prospective trials [published online November 8, 2019] J Thorac Oncol. doi: 10.1016/j.jtho.2019.10.015
  2. Alectinib (Alecensa®) [package insert]. South San Francisco, CA: Genentech, Inc.; 2018.

This article originally appeared on Cancer Therapy Advisor