Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: A randomized, multicenter phase II trial
- Authors
- Kim, D.-W.[Kim, D.-W.]; Tiseo, M.[Tiseo, M.]; Ahn, M.-J.[Ahn, M.-J.]; Reckamp, K.L.[Reckamp, K.L.]; Hansen, K.H.[Hansen, K.H.]; Kim, S.-W.[Kim, S.-W.]; Huber, R.M.[Huber, R.M.]; West, H.L.[West, H.L.]; Groen, H.J.M.[Groen, H.J.M.]; Hochmair, M.J.[Hochmair, M.J.]; Leighl, N.B.[Leighl, N.B.]; Gettinger, S.N.[Gettinger, S.N.]; Langer, C.J.[Langer, C.J.]; Rodríguez, L.G.P.-A.[Rodríguez, L.G.P.-A.]; Smit, E.F.[Smit, E.F.]; Kim, E.S.[Kim, E.S.]; Reichmann, W.[Reichmann, W.]; Haluska, F.G.[Haluska, F.G.]; Kerstein, D.[Kerstein, D.]; Camidge, D.R.[Camidge, D.R.]
- Issue Date
- 2017
- Publisher
- American Society of Clinical Oncology
- Citation
- Journal of Clinical Oncology, v.35, no.22, pp.2490 - 2498
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Clinical Oncology
- Volume
- 35
- Number
- 22
- Start Page
- 2490
- End Page
- 2498
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/30945
- DOI
- 10.1200/JCO.2016.71.5904
- ISSN
- 0732-183X
- Abstract
- Purpose: Most crizotinib-treated patients with anaplastic lymphoma kinase gene (ALK)-rearranged non-smallcell 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 progressionfree survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety. © 2017 by American Society of Clinical Oncology.
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