Reference Detail

Ref Type Journal Article
PMID (28475456)
Authors Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR
Title Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 35
Issue 22
Date 2017 Aug 01
Abstract Text Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib FDA approved Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in crizotinib-treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716). 27836716
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulted in objective response in 17% (3/18) and stable disease in 50% (9/18) of patients with alectinib-refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as subsequent therapy for ALK rearranged non-small cell lung cancer patients whose disease progressed after Xalkori (crizotinib) therapy ( detail...