Universität zu Köln

Novello, S., Mazieres, J., Oh, I-J., de Castro, J., Migliorino, M. R., Helland, A., Dziadziuszko, R., Griesinger, F., Kotb, A., Zeaiter, A., Cardona, A., Balas, B., Johannsdottir, H. K., Das-Gupta, A. and Wolf, J. (2018). Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann. Oncol., 29 (6). S. 1409 - 1417. OXFORD: OXFORD UNIV PRESS. ISSN 1569-8041

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Abstract

Background This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Results Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4 months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P < 0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade >= 3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks). Conclusion Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Novello, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazieres, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oh, I-J. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Castro, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Migliorino, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Helland, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dziadziuszko, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesinger, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotb, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeaiter, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cardona, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Balas, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Johannsdottir, H. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Das-Gupta, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183204
DOI:	10.1093/annonc/mdy121
Journal or Publication Title:	Ann. Oncol.
Volume:	29
Number:	6
Page Range:	S. 1409 - 1417
Date:	2018
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1569-8041
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRAIN METASTASES; OPEN-LABEL; PROGRESSION; SURVIVAL; TRIAL Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18320