Double Dosage of ALK Inhibitor Improves Outcomes in NSCLC

Increasing the standard dose of an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of non-small cell lung cancer (NSCLC) improves objective response rates (ORR) by 9% with limited additional toxicity, according to a study published in the Journal of Clinical Oncology (August 2017;35[22]:2490-2498).


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A majority of patients with ALK-positive NSCLC who are treated with crizotinib eventually experience disease progression, most often in the brain. A next-generation ALK inhibitor—brigatinib—may help to improve response rates in crizotinib-refractory disease.

Dong-Wan Kim, MD, PhD, Seoul National University Hospital (South Korea), and colleagues conducted a study to compare standard dosing with increased dosing of brigatinib in patients with crizotinib-refractory ALK-positive NSCLC. A total of 222 patients— stratified by brain metastases and best response to crizotinibwere randomly assigned (1:1) to receive oral brigatinib 90 mg once daily (arm A, n = 112) or 180 mg once daily (arm B, n = 110) with a 7-day lead-in at 90 mg. ORR was the primary endpoint.

Researchers acknowledged that at baseline, 154 patients (69%) had brain metastases and 164 patients (74%) had received prior chemotherapy.

After an 8-month follow-up, investigator-assessed ORR was 45% (97.5% CI, 34%-56%) in arm A and 54% (97.5% CI, 43%-65%) in arm B. Similarly, median progression-free survival was 9.2 months (95% CI, 7.4-15.6) in arm A compared with 12.9 months (95% CI, 11.1 to not reached) in arm B.

Independent review committee assessment showed that intracranial ORR in patients with baseline brain metastases was 42% in arm A and 67% in arm B.

Common adverse events resulting from brigatinib therapy in either arm included nausea, diarrhea, headache, and cough, though almost all cases of such events were grades 1 to 2.

Researchers concluded that a double dosage of brigatinib showed consistently-improved whole-body and intracranial responses as well as robust progression-free survival compared with standard 90 mg dosage. “On the basis of these results, brigatinib seems to be a promising new treatment option for crizotinib-refractory ALK-positive NSCLC,” they wrote.—Zachary Bessette