Alunbrig (brigatinib)

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors.

P1/2, N=65, Recruiting, Princess Maxima Center for Pediatric Oncology | Trial completion date: Dec 2030 --> Dec 2033 | Trial primary completion date: Dec 2029 --> Dec 2033

This study is by far the most comprehensive systematic review and meta-analysis on HRQoL among ALK-positive NSCLC patients treated with ALK-TKIs. These findings extended prior literature by conducting a granular comparison of all available ALK-TKIs across multiple endpoints and highlighted the improved performance of next-generation ALK-TKIs in enhancing HRQoL for ALK-positive NSCLC patients.

Sensitivity analyses confirmed that none of the ALK inhibitors were cost-effective compared to chemotherapy. The five-year BIA estimated the budget impact of ceritinib (450 mg/day, 750 mg/day), alectinib (600 mg/day, 1,200 mg/day), and brigatinib at 2,345 (63.81), 3,703 (100.76), 9,830 (267.49), 19,328 (525.92), and 9,502 (258.56) million THB (USD), respectively.

This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21). For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

P2, N=110, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial primary completion date: Apr 2025 --> Sep 2025

However, this response is not observed when BET inhibitors are combined with brigatinib, a multi-kinase inhibitor in clinical use. These findings highlight the complex cellular adaptations in schwannomas and suggest that targeting BET alongside MEK inhibition prevents resistance mechanisms and promotes cell death.

Despite the approval to date of 3 generations of ALK tyrosine kinase inhibitors (TKIs) and the clinical development of a 4th-generation ALK TKI, neladalkib (NVL-655), patients still eventually progress on sequential treatment of various generations of ALK TKIs...Since then, she has been treated with multiple ALK TKIs including crizotinib, alectinib, brigatinib, and lorlatinib sequentially (from age 75 to 80) but requiring dose reduction and interruption of lorlatinib due to neurocognitive toxicity from previous stereotactic brain radiation and resection and eventual discontinuation of lorlatinib...This is the first patient case report with >24 months on-going follow-up demonstrating that gilteritinib could be repurposed as a potent and tolerable ALK inhibitor based on previously reported pre-clinical activity and with potential CNS activity. A Phase 2 trial of gilteritnib in alectinib- or lorlatinib-refractory ALK+ NSCLC is being planned (NCT07140016).

The corresponding PDO model demonstrated sensitivity to a combination of pemetrexed, carboplatin, and osimertinib, but insensitivity to osimertinib monotherapy...The patient had progressed on multiple lines of therapy, including alectinib and lorlatinib. The PDO model showed sensitivity to brigatinib but insensitivity to ensartinib. Subsequent treatment with brigatinib induced a PR that was sustained for 5.8 months; the patient survived for a total of 9 months following the initiation of this PDO-guided therapy. These two cases suggests that PDOs derived from primary and metastatic lesions may help optimize treatment regimens for patients with lung cancer brain metastases, thereby enabling personalized therapy and potentially improving survival outcomes.

This integrated analysis showed that brigatinib has clinically meaningful activity after disease progression on alectinib.

This is the first study to identify sex differences in ALK-TKI-associated cardiotoxicity, highlighting a consistent female predominance in reported adverse events. In particular, considering its widespread use and the clinical importance of left ventricular failure, the pronounced disproportionality signal of cardiotoxicity in females associated with alectinib is thought to have substantial clinical impact. These results underscore the need for heightened clinical vigilance and further research into sex-specific risk stratification and preventive strategies for cardiotoxicity in patients receiving ALK-TKIs.