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

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art_SORIA_Firstline_ceritinib_versus_platinumbased_chemotherapy_in_advanced_ALKrearranged_2017.PDF (667.62 KB)
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946
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
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Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
SORIA, Jean-Charles
TAN, Daniel S. W.
CHIARI, Rita
WU, Yi-Long
PAZ-ARES, Luis
WOLF, Juergen
GEATER, Sarayut L.
ORLOV, Sergey
CORTINOVIS, Diego
YU, Chong-Jen
Citação
LANCET, v.389, n.10072, p.917-929, 2017
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
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.
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https://observatorio.fm.usp.br/handle/OPI/18977
Referências
  1. Camidge DR, 2011, J THORAC ONCOL, V6, P774, DOI 10.1097/JTO.0b013e31820cf053
  2. Ciuleanu T, 2009, LANCET, V374, P1432, DOI 10.1016/S0140-6736(09)61497-5
  3. Dziadziuszko R, 2016, WORLD C LUNG CANC VI
  4. Felip E, 2016, ANN ONCOL S, V27
  5. Friboulet L, 2014, CANCER DISCOV, V4, P662, DOI 10.1158/2159-8290.CD-13-0846
  6. Gettinger SN, 2016, LANCET ONCOL, V17, P1683, DOI 10.1016/S1470-2045(16)30392-8
  7. Hida T, LANCET IN PRESS
  8. Hong Y, 2016, J CLIN PHARMACOL, DOI [10.1002/jcph.849, DOI 10.1002/JCPH.849]
  9. Katayama R, 2012, SCI TRANSL MED, V4, DOI 10.1126/scitranslmed.3003316
  10. Kim DE, 2016, INT J PRECIS ENG MAN, V17, P1
  11. Kim Y, 2016, WORLD C LUNG CANC VI
  12. Lee JO, 2011, J THORAC ONCOL, V6, P1474, DOI 10.1097/JTO.0b013e3182208fc2
  13. Zykadia prescribing information, 2014, ZYK PRESCR INF
  14. Otterson GA, 2012, J CLIN ONCOL, V30
  15. Paz-Ares L, 2012, LANCET ONCOL, V13, P247, DOI 10.1016/S1470-2045(12)70063-3
  16. Paz-Ares LG, 2013, J CLIN ONCOL, V31, P2895, DOI 10.1200/JCO.2012.47.1102
  17. Peters S, 2014, ANN ONCOL, V25
  18. Scagliotti GV, 2008, J CLIN ONCOL, V26, P3543, DOI 10.1200/JCO.2007.15.0375
  19. Scagliotti GV, 2005, CLIN CANCER RES, V11, P690
  20. Shaw AT, 2014, NEW ENGL J MED, V370, P1189, DOI 10.1056/NEJMoa1311107
  21. Shaw AT, 2009, J CLIN ONCOL, V27, P4247, DOI 10.1200/JCO.2009.22.6993
  22. Soda M, 2007, NATURE, V448, P561, DOI 10.1038/nature05945
  23. Solomon BJ, 2016, J CLIN ONCOL, V34, P2858, DOI 10.1200/JCO.2015.63.5888
  24. Solomon BJ, 2014, NEW ENGL J MED, V371, P2167, DOI 10.1056/NEJMoa1408440
  25. Zhang I, 2015, LANCET ONCOL, V16, pE510, DOI 10.1016/S1470-2045(15)00013-3

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03