Jean-Charles Soria1, Daniel S W Tan2, Rita Chiari3, Yi-Long Wu4, Luis Paz-Ares5, Juergen Wolf6, Sarayut L Geater7, Sergey Orlov8, Diego Cortinovis9, Chong-Jen Yu10, Maximillian Hochmair11, Alexis B Cortot12, Chun-Ming Tsai13, Denis Moro-Sibilot14, Rosario G Campelo15, Tracey McCulloch16, Paramita Sen16, Margaret Dugan16, Serafino Pantano17, Fabrice Branle17, Cristian Massacesi17, Gilberto de Castro18. 1. University Paris-Sud, Orsay, France; Institut Gustave Roussy, Villejuif, France. Electronic address: Jean-Charles.Soria@gustaveroussy.fr. 2. National Cancer Centre Singapore and Genome Institute of Singapore, Singapore. 3. Azienda Ospedale Perugia, Perugia, Italy. 4. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. 5. University Hospital Virgen del RocioDoce de Octubre, Universidad Complutense & CNIO, Madrid, Spain. 6. University Hospital Cologne, Cologne, Germany. 7. Songklanagarind Hospital, Songkla, Thailand. 8. State Pavlov Medical University, St Petersburg, Russia. 9. Az. Ospedaliera San Gerardo, Monza, Italy. 10. National Taiwan University Hospital, Taipei, Taiwan. 11. Respiratory Oncology Unit, Department of Respiratory and Critical Care Medicine, Otto-Wagner-Spital, Vienna, Austria. 12. CHU de LILLE, Lille, France. 13. Taipei Veterans General Hospital, Taipei, Taiwan. 14. Hôpital Albert Michallon, Grenoble, France. 15. University Hospital A Coruña, La Coruna, Spain. 16. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 17. Novartis Pharma AG, Basel, Switzerland. 18. Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
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/m2 or carboplatin AUC 5-6 plus pemetrexed 500 mg/m2] 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. FUNDING: Novartis Pharmaceuticals Corporation.
RCT Entities:
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/m2 or carboplatin AUC 5-6 plus pemetrexed 500 mg/m2] 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. FUNDING: Novartis Pharmaceuticals Corporation.
Authors: Malinda Itchins; Brandon Lau; Amanda L Hudson; Helen Westman; Cathy Yi Xia; Sarah A Hayes; Viive M Howell; Michael Rodriguez; Wendy A Cooper; Heng Wei; Michael Buckland; Bob T Li; Mark Li; Vivek Rathi; Stephen B Fox; Anthony J Gill; Stephen J Clarke; Michael J Boyer; Nick Pavlakis Journal: Oncologist Date: 2020-07-02
Authors: Aaron N Hata; Alice T Shaw; Satoshi Yoda; Jessica J Lin; Michael S Lawrence; Benjamin J Burke; Luc Friboulet; Adam Langenbucher; Leila Dardaei; Kylie Prutisto-Chang; Ibiayi Dagogo-Jack; Sergei Timofeevski; Harper Hubbeling; Justin F Gainor; Lorin A Ferris; Amanda K Riley; Krystina E Kattermann; Daria Timonina; Rebecca S Heist; A John Iafrate; Cyril H Benes; Jochen K Lennerz; Mari Mino-Kenudson; Jeffrey A Engelman; Ted W Johnson Journal: Cancer Discov Date: 2018-04-12 Impact factor: 39.397