T Reiman1, R Lai2, A S Veillard3, E Paris3, J C Soria4, R Rosell5, M Taron5, S Graziano6, R Kratzke7, L Seymour8, F A Shepherd9, J P Pignon3, P Sève10. 1. Department of Medicine, Dalhousie University and Department of Oncology, Saint John Regional Hospital, Saint John. Electronic address: Anthony.Reiman@HorizonNB.ca. 2. Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, Canada; Departments of. 3. Biostatistics and Epidemiology. 4. Medicine, Institut Gustave-Roussy, Paris, France. 5. Department of Medicine, Institut Catala d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. 6. Department of Medicine, State University of New York, Upstate Medical University, Syracuse. 7. Department of Medicine, University of Minnesota, Minneapolis, USA. 8. NCIC Clinical Trials Group, Kingston. 9. Department of Medicine, Princess Margaret Hospital, University Health Network, Toronto, Canada. 10. Department of Internal Medicine, Hopital de la Croix Rousse.
Abstract
BACKGROUND: The IALT, JBR.10, ANITA and Cancer and Leukemia Group B 9633 trials compared adjuvant chemotherapy with observation for patients with resected non-small-cell lung cancer (R-NSCLC). Data from the metastatic setting suggest high tumor class III beta-tubulin (TUBB3) expression is a determinant of insensitivity to tubulin-targeting agents (e.g. vinorelbine, paclitaxel). In 265 patients from JBR.10 (vinorelbine-cisplatin versus observation), high TUBB3 was an adverse prognostic factor and was associated (nonsignificantly) with 'greater' survival benefit from chemotherapy. We explored this further in additional patients from JBR.10 and the other three trials. PATIENTS AND METHODS: TUBB3 immunohistochemical staining was scored for 1149 patients on the four trials. The original JBR.10 cut-off scores were used to classify tumors as TUBB3 high or low. The prognostic and predictive value of TUBB3 on disease-free survival (DFS) and overall survival (OS) was assessed by Cox models stratified by trial and adjusted for clinical factors. RESULTS: High TUBB3 expression was prognostic for OS [hazard ratio (HR)=1.27 (1.07-1.51), P=0.008) and DFS [HR=1.30 (1.11-1.53), P=0.001). TUBB3 was not predictive of a differential treatment effect [interaction P=0.20 (OS), P=0.23 (DFS)]. Subset analysis (n=420) on vinorelbine-cisplatin gave similar results. CONCLUSIONS: The prognostic effect of high TUBB3 expression in patients with R-NSCLC has been validated. We were unable to confirm a predictive effect for TUBB3.
BACKGROUND: The IALT, JBR.10, ANITA and Cancer and Leukemia Group B 9633 trials compared adjuvant chemotherapy with observation for patients with resected non-small-cell lung cancer (R-NSCLC). Data from the metastatic setting suggest high tumorclass III beta-tubulin (TUBB3) expression is a determinant of insensitivity to tubulin-targeting agents (e.g. vinorelbine, paclitaxel). In 265 patients from JBR.10 (vinorelbine-cisplatin versus observation), high TUBB3 was an adverse prognostic factor and was associated (nonsignificantly) with 'greater' survival benefit from chemotherapy. We explored this further in additional patients from JBR.10 and the other three trials. PATIENTS AND METHODS: TUBB3 immunohistochemical staining was scored for 1149 patients on the four trials. The original JBR.10 cut-off scores were used to classify tumors as TUBB3 high or low. The prognostic and predictive value of TUBB3 on disease-free survival (DFS) and overall survival (OS) was assessed by Cox models stratified by trial and adjusted for clinical factors. RESULTS: High TUBB3 expression was prognostic for OS [hazard ratio (HR)=1.27 (1.07-1.51), P=0.008) and DFS [HR=1.30 (1.11-1.53), P=0.001). TUBB3 was not predictive of a differential treatment effect [interaction P=0.20 (OS), P=0.23 (DFS)]. Subset analysis (n=420) on vinorelbine-cisplatin gave similar results. CONCLUSIONS: The prognostic effect of high TUBB3 expression in patients with R-NSCLC has been validated. We were unable to confirm a predictive effect for TUBB3.
Authors: Jean-Yves Douillard; Rafael Rosell; Mario De Lena; Francesco Carpagnano; Rodryg Ramlau; Jose Luis Gonzáles-Larriba; Tomasz Grodzki; Jose Rodrigues Pereira; Alain Le Groumellec; Vito Lorusso; Claude Clary; Antonio J Torres; Jabrail Dahabreh; Pierre-Jean Souquet; Julio Astudillo; Pierre Fournel; Angel Artal-Cortes; Jacek Jassem; Leona Koubkova; Patricia His; Marcello Riggi; Patrick Hurteloup Journal: Lancet Oncol Date: 2006-09 Impact factor: 41.316
Authors: Gary M Strauss; James E Herndon; Michael A Maddaus; David W Johnstone; Elizabeth A Johnson; David H Harpole; Heidi H Gillenwater; Dorothy M Watson; David J Sugarbaker; Richard L Schilsky; Everett E Vokes; Mark R Green Journal: J Clin Oncol Date: 2008-09-22 Impact factor: 44.544
Authors: Pascal Sève; Raymond Lai; Keyue Ding; Timothy Winton; Charles Butts; John Mackey; Charles Dumontet; Laith Dabbagh; Sarit Aviel-Ronen; Lesley Seymour; Marlo Whitehead; Ming-Sound Tsao; Frances A Shepherd; Tony Reiman Journal: Clin Cancer Res Date: 2007-02-01 Impact factor: 12.531
Authors: Rafael Rosell; Giorgio Scagliotti; Kathleen D Danenberg; Reginald V N Lord; Gerold Bepler; Silvia Novello; Janine Cooc; Lucio Crinò; José Javier Sánchez; Miquel Taron; Corrado Boni; Filippo De Marinis; Maurizio Tonato; Maurizio Marangolo; Felice Gozzelino; Franceso Di Costanzo; Massimo Rinaldi; Dennis Salonga; Craig Stephens Journal: Oncogene Date: 2003-06-05 Impact factor: 9.867
Authors: Maria T Baquero; Jason A Hanna; Veronique Neumeister; Huan Cheng; Annette M Molinaro; Lyndsay N Harris; David L Rimm Journal: Cancer Date: 2012-02-22 Impact factor: 6.860
Authors: Karen Kelly; Kari Chansky; Philip C Mack; Primo N Lara; Fred R Hirsch; Wilbur A Franklin; Antoinette J Wozniak; Martin J Edelman; Stephen K Williamson; David R Gandara Journal: Clin Lung Cancer Date: 2013-07-31 Impact factor: 4.785
Authors: Luc Friboulet; Ken André Olaussen; Jean-Pierre Pignon; Frances A Shepherd; Ming-Sound Tsao; Stephen Graziano; Robert Kratzke; Jean-Yves Douillard; Lesley Seymour; Robert Pirker; Martin Filipits; Fabrice André; Eric Solary; Florence Ponsonnailles; Angélique Robin; Annabelle Stoclin; Nicolas Dorvault; Frédéric Commo; Julien Adam; Elsa Vanhecke; Patrick Saulnier; Jürgen Thomale; Thierry Le Chevalier; Ariane Dunant; Vanessa Rousseau; Gwénaël Le Teuff; Elisabeth Brambilla; Jean-Charles Soria Journal: N Engl J Med Date: 2013-03-21 Impact factor: 91.245
Authors: Federico Rotolo; Chang-Qi Zhu; Elisabeth Brambilla; Stephen L Graziano; Ken Olaussen; Thierry Le-Chevalier; Jean-Pierre Pignon; Robert Kratzke; Jean-Charles Soria; Frances A Shepherd; Lesley Seymour; Stefan Michiels; Ming-Sound Tsao Journal: Transl Lung Cancer Res Date: 2018-06