IASLC 2017: Brigatinib in ALK-Positive Non–Small Cell Lung Cancer
Data from the phase II ALTA clinical trial evaluating brigatinib (Alunbrig) in patients with locally advanced or metastatic anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC) who have disease progression on crizotinib were presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC). The presentation shared updated safety and efficacy data from the trial as of February 21, 2017, which continue to support previously reported clinical results.
The randomized phase II ALTA trial was designed to investigate the efficacy and safety of brigatinib at two dosing regimens. Patients received either 90 mg of brigatinib once daily (n = 112; arm A) or 180 mg once daily following a 7-day lead-in of 90 mg once daily (n = 110; arm B).
“The data being presented at the WCLC provide further evidence supporting the role of brigatinib in the treatment of patients with advanced ALK-positive NSCLC,” said David Kerstein, MD, Senior Medical Director and Global Clinical Lead for brigatinib, Oncology Clinical Research, Takeda. “There continues to be an unmet need for the more than 30,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year. We are encouraged by the updated data from the ALTA trial, which support the efficacy and safety of brigatinib in a crizotinib-refractory population, at the dosing regimen that is being taken forward into ongoing and future clinical trials.”
“The updated data from the ALTA trial further support the clinical benefit of brigatinib,” said Myung-Ju Ahn, MD, Professor, Department of Hematology & Oncology, Samsung Medical Center. “I am especially encouraged by the efficacy seen in patients with brain metastases.... The central nervous system is a common site for progression in this disease, with brain metastases occurring in up to 70% of patients after treatment with crizotinib. With the 180-mg dosing regimen of brigatinib, two-thirds of patients with measurable brain metastases had an intracranial response, with a median intracranial duration of response of 16.6 months.”
Key Findings
As of February 21, 2017, at a median follow-up of 16.8 and 18.6 months in arms A and B, respectively, 32% of patients in arm A and 41% of patients in arm B continued to receive brigatinib.
The investigator-assessed confirmed objective response rate, which was the primary endpoint, was 46% in arm A and 55% in arm B. Per independent review committee (IRC), the confirmed objective response rate was 51% in arm A and 55% in arm B. Investigator-assessed median duration of response was 12 months in arm A and 13.8 months in arm B. IRC-assessed median duration of response was 13.8 months in arm A and 14.8 months in arm B.
Investigator-assessed median progression-free survival was 9.2 months in arm A and 15.6 months in arm B. IRC-assessed median progression-free survival was 9.2 months in arm A and 16.7 months in arm B. Median overall survival was not reached in arm A and 27.6 months in arm B. The 1-year overall survival probability was 70% in arm A and 80% in arm B.
Of the patients with measurable brain metastases at baseline (n = 26 and 18 in arm A and arm B, respectively), 50% in arm A and 67% in arm B achieved a confirmed intracranial objective response by IRC assessment. The median duration of intracranial response was not reached in arm A and was 16.6 months in arm B. In patients with any brain metastases at baseline, the median intracranial progression-free survival as assessed by the IRC was 12.8 months in arm A and 18.4 months in arm B.
The most common grade ≥ 3 treatment-related adverse events in arm A and arm B included increased blood creatine phosphokinase (3% and 11%), hypertension (4% and 4%), increased lipase (4% and 4%), pneumonitis (2% and 4%), and rash (1% and 4%). Dose reduction due to adverse events was reported in 9% and 30% of the two groups, and treatment discontinuation due to adverse events occurred in 4% and 11%.
The efficacy and safety data from the ALTA trial continue to support future trials with the 180-mg dosing regimen.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
