Brigatinib for Second-Line Treatment After Progression on Crizotinib

Brigatinib for Second-Line Treatment After Progression on Crizotinib

Although targeted therapy has brought hope to patients with ALK-positive NSCLC, unfortunately, even after treatment, the cancer may still progress or develop resistance over time. When a patient no longer responds to initial therapy (e.g., crizotinib), a change in treatment regimen is necessary. To address this, another clinical study of brigatinib specifically enrolled 222 patients with ALK-positive metastatic NSCLC whose disease had worsened after receiving crizotinib. These patients were divided into two groups: 112 patients received brigatinib at a daily dose of 90mg (without dose escalation); the other 110 patients received the recommended dosing regimen, i.e., 90mg daily for the first 7 days, followed by an increase to 180mg daily.

Tumor Response Data

p>    The study results showed that among patients receiving the recommended dosing regimen (i.e., transitioning from 90mg to 180mg), more than half achieved a positive treatment response. Specifically, among the 110 patients on this regimen, 58 (53%) achieved tumor shrinkage or disappearance. Among them, 5 patients (4.5%) achieved complete remission, meaning no detectable tumor on imaging; another 53 patients (48%) achieved partial remission, i.e., significant tumor shrinkage. In the 112 patients receiving the fixed 90mg dose (without escalation), 54 (48%) also achieved remission, including 4 complete remissions and 50 partial remissions. The median duration of response was 13.8 months in both dose groups, indicating durable efficacy.

Efficacy in Brain Metastases in Second-Line Treatment

This second-line study also evaluated the efficacy of brigatinib in patients with brain metastases. Among patients receiving the recommended dosing regimen (90mg→180mg), 18 had measurable brain metastases. Results showed that 12 of these patients (67%, i.e., nearly 2 out of every 3 patients) experienced shrinkage of brain tumors. Although no patient achieved complete remission in the brain, the partial response rate was 67%. Among these 12 patients who responded to brigatinib in the brain, 6 had responses lasting 6 months or longer, and 3 had responses lasting 12 months or longer. In the fixed 90mg dose group, 11 of 26 patients with brain metastases (42%) experienced brain tumor shrinkage, including 2 complete remissions and 9 partial remissions. These data again confirm that even after crizotinib treatment failure, brigatinib can effectively control metastatic lesions, including those in the brain.