Universität zu Köln

Wolf, J., Helland, A., Oh, I-J, Migliorino, M. R., Dziadziuszko, R., Wrona, A., de Castro, J., Mazieres, J., Griesinger, F., Chlistalla, M., Cardona, A., Ruf, T., Trunzer, K., Smoljanovic, V and Novello, S. (2022). Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. ESMO Open, 7 (1). AMSTERDAM: ELSEVIER. ISSN 2059-7029

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Abstract

Background: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. Patients and methods: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2), every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. Results: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). Conclusions: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wolf, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Helland, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oh, I-J UNSPECIFIED UNSPECIFIED UNSPECIFIED Migliorino, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dziadziuszko, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wrona, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Castro, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazieres, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Griesinger, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chlistalla, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cardona, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruf, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Trunzer, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smoljanovic, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Novello, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-693028
DOI:	10.1016/j.esmoop.2021.100333
Journal or Publication Title:	ESMO Open
Volume:	7
Number:	1
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2059-7029
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SURVIVAL Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69302