Non-Small Cell Lung Cancer Coverage from Every Angle

EML4-ALK Mutations and Lorlatinib Treatment in Lung Cancer

By: Kayci Reyer
Posted: Wednesday, July 1, 2020

According to research presented as part of the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting I (Abstract CT025), patients with ALK-positive non–small cell lung cancer who have a variant of an EML4-ALK mutation may experience increased benefits of treatment with the ALK tyrosine kinase inhibitor lorlatinib. The phase II study included patients who had undergone prior treatment with a second-generation ALK inhibitor and who had received 100 mg of lorlatinib daily (the recommended phase II dose).

“The presence of an ALK resistance mutation might enrich for EML4-ALK variants 1 and 3. Lapatinib exhibited antitumor activity irrespective of EML4-ALK variant and across a variety of ALK-resistance mutations,” concluded Todd M. Bauer, MD, of the Sarah Cannon Cancer Research Institute, Nashville, and colleagues.

The study included baseline plasma samples collected from 156 patients and evaluated EML4-ALK variant and ALK kinase domain mutations using circulating free DNA analysis. A total of 64 patients (41.0%) had ALK fusions, with EML4-ALK variants 1, 2, and 3 identified in 17.3%, 2.6%, and 15.4%, respectively, and variations 4, 5, 7, and 8 appearing in a total of 3.2%. Overall, 40 patients had ALK-resistance mutations, with EML4-ALK variant 1 occurring in 6, variant 2 occurring in 1, and variant 3 occurring in 18.

The overall response rate was 33.3% for patients with variant 1, 75.0% for those with variant 2, and 45.8% for patients with variant 3. Patients with variant 1 experienced a similar duration of response as those with variant 3 (6.9 months). The median duration of response for patients with variant 2 was not reached. Patients of other variant types did not achieve an observable response. More than half of patients (n = 92) had no ALK fusions in the circulating free DNA; the overall response rate for this subset was 39.1%, with a median duration of response of 7.1 months.

Disclosure: For full disclosures by the study authors, visit

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