Universität zu Köln

Janne, Pasi A., van den Heuvel, Michel M., Barlesi, Fabrice, Cobo, Manuel, Mazieres, Julien, Crino, Lucio, Orlov, Sergey ORCID: 0000-0001-6080-8042, Blackhall, Fiona ORCID: 0000-0001-8716-3395, Wolf, Juergen, Garrido, Pilar, Poltoratskiy, Artem, Mariani, Gabriella, Ghiorghiu, Dana, Kilgour, Elaine, Smith, Paul, Kohlmann, Alexander, Carlile, David J., Lawrence, David, Bowen, Karin and Vansteenkiste, Johan (2017). Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer The SELECT-1 Randomized Clinical Trial. JAMA-J. Am. Med. Assoc., 317 (18). S. 1844 - 1854. CHICAGO: AMER MEDICAL ASSOC. ISSN 1538-3598

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Abstract

IMPORTANCE There are no specifically approved targeted therapies for the most common genomically defined subset of non-small cell lung cancer (NSCLC), KRAS-mutant lung cancer. OBJECTIVE To compare efficacy of the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel alone as a second-line therapy for advanced KRAS-mutant NSCLC. DESIGN, SETTING, AND PARTICIPANTS Multinational, randomized clinical trial conducted at 202 sites across 25 countries from October 2013 through January 2016. Of 3323 patients with advanced NSCLC and disease progression following first-line anticancer therapy tested for a KRAS mutation, 866 were enrolled and 510 randomized. Primary reason for exclusion was ineligibility. The data cutoff date for analysis was June 7, 2016. INTERVENTIONS Patients were randomized 1: 1; 254 to receive selumetinib + docetaxel and 256 to receive placebo + docetaxel. MAIN OUTCOMES AND MEASURES Primary end point was investigator assessed progression-free survival. Secondary end points included overall survival, objective response rate, duration of response, effects on disease-related symptoms, safety, and tolerability. RESULTS Of 510 randomized patients (mean age, 61.4 years [SD, 8.3]; women, 207 [41%]), 505 patients (99%) received treatment and completed the study (251 received selumetinib + docetaxel; 254 received placebo + docetaxel). At the time of data cutoff, 447 patients (88%) had experienced a progression event and 346 deaths (68%) had occurred. Median progression-free survival was 3.9 months (interquartile range [IQR], 1.5-5.9) with selumetinib + docetaxel and 2.8 months (IQR, 1.4-5.5) with placebo + docetaxel (difference, 1.1 months; hazard ratio [HR], 0.93 [95% CI, 0.77-1.12]; P =.44). Median overall survivalwas 8.7 months (IQR, 3.6-16.8) with selumetinib + docetaxel and 7.9 months (IQR, 3.8-20.1) with placebo + docetaxel (difference, 0.9 months; HR, 1.05 [95% CI, 0.85-1.30]; P =.64). Objective response rate was 20.1% with selumetinib + docetaxel and 13.7% with placebo + docetaxel (difference, 6.4%; odds ratio, 1.61 [95% CI, 1.00-2.62]; P =.05). Median duration of response was 2.9 months (IQR, 1.7-4.8; 95% CI, 2.7-4.1) with selumetinib + docetaxel and 4.5 months (IQR, 2.3-7.3; 95% CI, 2.8-5.6) with placebo + docetaxel. Adverse events of grade 3 or higher were more frequent with selumetinib + docetaxel (169 adverse events [67%] for selumetinib + docetaxel vs 115 adverse events [45%] for placebo + docetaxel; difference, 22%). CONCLUSIONS AND RELEVANCE Among patients with previously treated advanced KRAS-mutant non-small cell lung cancer, addition of selumetinib to docetaxel did not improve progression-free survival compared with docetaxel alone.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Janne, Pasi A. UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, Michel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barlesi, Fabrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Cobo, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazieres, Julien UNSPECIFIED UNSPECIFIED UNSPECIFIED Crino, Lucio UNSPECIFIED UNSPECIFIED UNSPECIFIED Orlov, Sergey UNSPECIFIED orcid.org/0000-0001-6080-8042 UNSPECIFIED Blackhall, Fiona UNSPECIFIED orcid.org/0000-0001-8716-3395 UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Garrido, Pilar UNSPECIFIED UNSPECIFIED UNSPECIFIED Poltoratskiy, Artem UNSPECIFIED UNSPECIFIED UNSPECIFIED Mariani, Gabriella UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghiorghiu, Dana UNSPECIFIED UNSPECIFIED UNSPECIFIED Kilgour, Elaine UNSPECIFIED UNSPECIFIED UNSPECIFIED Smith, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohlmann, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Carlile, David J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lawrence, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Bowen, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Vansteenkiste, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-231274
DOI:	10.1001/jama.2017.3438
Journal or Publication Title:	JAMA-J. Am. Med. Assoc.
Volume:	317
Number:	18
Page Range:	S. 1844 - 1854
Date:	2017
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	1538-3598
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AZD6244 ARRY-142886; PHASE-II; MULTICENTER; MUTATIONS Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23127