Brigatinib, an investigational oral tyrosine kinase inhibitor demonstrated antitumor activity in crizotinib-treated and crizotinib-naïve patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), including those with brain metastases at the time of initial diagnosis.1
In a phase 1/2 trial, researchers enrolled patients with advanced malignancies, including 79 patients with ALK-positive NSCLC, of which 90% had received crizotinib. Participants received brigatinib 30 mg orally daily in increasing increments until the maximum tolerated dose was identified.
Results showed that among the 78 evaluable patients with NSCLC, the objective response rate was 74% (95% CI, 63 – 84). Among the 70 who received prior crizotinib and the 8 who were crizotinib-naïve, the objective response rate was 71% (95% CI, 59 – 82) and 100% (95% CI, 63 – 100), respectively.
Specifically, 4 patients who have previously received crizotinib and 3 crizotinib-naïve patients achieved a complete response; 46 and 5 patients, respectively, had partial responses. The median duration of response was 11.2 months for all patients with NSCLC.
The study further demonstrated that median progression-free survival was 11.2 months overall.
Researchers also found that among the 15 patients with measurable brain lesions, 53% achieved an intracranial response, with a median duration of intracranial response of 18.9 months. The intracranial disease control rate was 87%.
In terms of safety, the most common treatment-emergent adverse events were nausea (52%), fatigue (42%), diarrhea (40%), headache (33%), and cough (32%). Serious treatment-related adverse events included dyspnea (7%), pneumonia (6%), hypoxia (5%), pulmonary embolism (3%), and pyrexia (2%).
The safety and efficacy of brigatinib is also being evaluated in crizotinib-resistant patients with ALK-positive NSCLC in an ongoing, pivotal, phase 2 trial.
- Lena H, Rizvi NA, Wolf J, et al. Brigatinib efficacy and safety in patients (pts) with anaplastic lymphoma kinase (ALK)-positive (ALK+) non-small cell lung cancer (NSCLC) in a phase 1/2 trial. Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.