Non-Small Cell Lung Cancer Coverage from Every Angle
Advertisement
Advertisement

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 abstractsonline.com.



By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.