Universität zu Köln

Soria, Jean-Charles, Tan, Daniel S. W., Chiari, Rita, Wu, Yi-Long ORCID: 0000-0002-3611-0258, Paz-Ares, Luis, Wolf, Juergen, Geater, Sarayut L., Orlov, Sergey ORCID: 0000-0001-6080-8042, Cortinovis, Diego, Yu, Chong-Jen ORCID: 0000-0001-5664-9392, Hochmair, Maximillian, Cortot, Alexis B., Tsai, Chun-Ming, Moro-Sibilot, Denis, Campelo, Rosario G., McCulloch, Tracey, Sen, Paramita, Dugan, Margaret, Pantano, Serafino, Branle, Fabrice, Massacesi, Cristian and de Castro, Gilberto, Jr. (2017). First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet, 389 (10072). S. 917 - 930. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1474-547X

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Abstract

Background The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients. Methods This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m(2) or carboplatin AUC 5-6 plus pemetrexed 500 mg/m(2)] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening. Investigators and patients were not masked to treatment assignment. The primary endpoint was blinded independent review committee assessed progression-free survival, based on all randomly assigned patients (the full analysis set). Efficacy analyses were done based on the full analysis set. All safety analyses were done based on the safety set, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01828099. Findings Between Aug 19, 2013, and May 11, 2015, 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187). Median progression-free survival (as assessed by blinded independent review committee) was 16.6 months (95% CI 12.6-27.2) in the ceritinib group and 8.1 months (5.8-11.1) in the chemotherapy group (hazard ratio 0.55 [95% CI 0.42-0.73]; p<0.00001). The most common adverse events were diarrhoea (in 160 [85%] of 189 patients), nausea (130 [69%]), vomiting (125 [66%]), and an increase in alanine aminotransferase (114 [60%]) in the ceritinib group and nausea (in 97 [55%] of 175 patients), vomiting (63 [36%]), and anaemia (62 [35%]) in the chemotherapy group. Interpretation First-line ceritinib showed a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Soria, Jean-Charles UNSPECIFIED UNSPECIFIED UNSPECIFIED Tan, Daniel S. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiari, Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Wu, Yi-Long UNSPECIFIED orcid.org/0000-0002-3611-0258 UNSPECIFIED Paz-Ares, Luis UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Geater, Sarayut L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Orlov, Sergey UNSPECIFIED orcid.org/0000-0001-6080-8042 UNSPECIFIED Cortinovis, Diego UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Chong-Jen UNSPECIFIED orcid.org/0000-0001-5664-9392 UNSPECIFIED Hochmair, Maximillian UNSPECIFIED UNSPECIFIED UNSPECIFIED Cortot, Alexis B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsai, Chun-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Moro-Sibilot, Denis UNSPECIFIED UNSPECIFIED UNSPECIFIED Campelo, Rosario G. UNSPECIFIED UNSPECIFIED UNSPECIFIED McCulloch, Tracey UNSPECIFIED UNSPECIFIED UNSPECIFIED Sen, Paramita UNSPECIFIED UNSPECIFIED UNSPECIFIED Dugan, Margaret UNSPECIFIED UNSPECIFIED UNSPECIFIED Pantano, Serafino UNSPECIFIED UNSPECIFIED UNSPECIFIED Branle, Fabrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Massacesi, Cristian UNSPECIFIED UNSPECIFIED UNSPECIFIED de Castro, Gilberto, Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236797
DOI:	10.1016/S0140-6736(17)30123-X
Journal or Publication Title:	Lancet
Volume:	389
Number:	10072
Page Range:	S. 917 - 930
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1474-547X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PEMETREXED PLUS CISPLATIN; CRIZOTINIB; PARAMOUNT Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23679