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Brigatinib in Alectinib-Resistant ALK-Positive NSCLC

By: Vanessa A. Carter, BS
Posted: Friday, March 26, 2021

Toyoaki Hida, MD, PhD, of Aichi Cancer Center Hospital, Japan, and colleagues presented their research regarding the use of ALK inhibitor brigatinib in alectinib-resistant, ALK-positive non–small cell lung cancer (NSCLC). The phase II J-ALTA trial findings, which suggested that brigatinib demonstrated “meaningful” activity in these patients, were presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer in Singapore (WCLC), held in virtual format in January 2021 (Abstract P75.01).

The study enrolled 72 patients with ALK-positive NSCLC who previously experienced disease progression on alectinib or other ALK tyrosine kinase inhibitors. Eligible plasma samples were obtained from 70 participants at baseline. The researchers analyzed samples for ALK kinase domain mutations and EML4-ALK fusion status.

A confirmed response to brigatinib was recorded in 30% of study participants. For 51 patients, alectinib was the most recent ALK tyrosine kinase inhibitor used for treatment, and 35.3% of them responded to brigatinib. In 15.7% of patients, secondary ALK mutations were discovered in plasma, with the objective response rate confirmed in five of these individuals. Best responses included five confirmed partial responses, four patients with stable disease, and two cases of progressive disease.

There were no secondary ALK mutations found in 84.2% of patients; an objective response was confirmed in 27.1% of them. Amplification of the MYC gene was recorded in one patient. Baseline EML4-ALK fusion was demonstrated in 51.4% of patients who previously received ALK tyrosine kinase inhibitor treatment, and 25.0% of these patients had secondary ALK mutations. At the end of brigatinib treatment, postbaseline samples were collected from 49 participants. Secondary ALK mutations were discovered in seven of these patients, and amplification of the MYC gene was recorded in two individuals.

Disclosure: For full disclosures of the study authors, visit wclc.iaslc.org.



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