S Novello1, V Torri2, C Grohe3, S Kurz4, M Serke5, T Wehler5, A Meyer6, D Ladage6, M Geissler7, I Colantonio8, C Cauchi8, E Stoelben9, A Ceribelli10, C Kropf-Sanchen11, G Valmadre12, G Borra13, M Schena14, A Morabito15, A Santo16, V Gregorc17, R Chiari18, M Reck19, G Schmid-Bindert20, G Folprecht21, F Griesinger22, A Follador23, P Pedrazzoli24, A Bearz25, O Caffo26, N J Dickgreber27, L Irtelli28, G Wiest29, V Monica30, L Porcu2, C Manegold31, G V Scagliotti30. 1. Department of Oncology at San Luigi Hospital, University of Torino, Orbassano (Torino), Italy. Electronic address: silvia.novello@unito.it. 2. Laboratory of Methodology for Clinical Research, Oncology Department at Instituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. 3. Department of Respiratory Diseases, Evangelische Lungenklinik Berlin, Berlin, Germany. 4. Evangelische Lungenklinik Berlin, Berlin, Germany. 5. Thorax Center Clinic for Haematology, Oncology, Pulmonology and Palliative Medicine, Evangelisches Krankenhaus Hamm, Hamm, Germany. 6. Department of Pneumology, Maria Hilf Hospital, Moenchengladbach, Germany. 7. Esslingen Cancer Center Department of Oncology, Gastroenterology and Infectious Diseases Klinikum Esslingen, Esslingen, Germany. 8. Division of Oncology, Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy. 9. Lung Clinic, Cologne-Merheim Hospital, Cologne, Germany. 10. Division of Clinical Oncology A, Istituto Nazionale Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy. 11. Department of Pulmonology, Internal Medicine II, University of Ulm, Ulm, Germany. 12. Division of Clinical Oncology, Ospedale di Sondalo, Sondrio, Italy. 13. Division of Clinical Oncology, AOU Maggiore della Carità, Novara, Italy. 14. Division of Clinical Oncology I, AOU Città della Salute e della Scienza, Turin, Italy. 15. Division of Clinical Oncology and Thoracic Pneumology, IRCCS Fondazione Pascale, Naples, Italy. 16. Complex Operative Unit of Oncology - Gruppo Interdisciplinare Veronese Oncologia Polmonare (GIVOP), Verona, Italy. 17. Division of Clinical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy. 18. Division of Clinical Oncology, Azienda Ospedaliera di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy. 19. Oncology Department, LungenClinic Grosshansdorf, Grosshansdorf, Germany. 20. Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 21. University Hospital Carl Gustav Carus Medical Department I Dresden, Dresden, Germany. 22. Clinic for Haematology and Oncoloy, Medizinischer Campus Universität Oldenburg, Oldenburg, Germany. 23. Department of Oncology, Presidio Ospedaliero Universitario Santa Maria della Misericordia, Azienda Sanitaria Universitaria Integrata Friuli Centrale, Udine, Italy. 24. Oncology Division, University Hospital Santa Maria della Misericordia AOU Friuli Centrale, Udine, Italy. 25. Division of Clinical Oncology, Centro di Riferimento Oncologico, Aviano, Italy. 26. Division of Clinical Oncology, Ospedale Santa Chiara, Trento, Italy. 27. Department for Respiratory Medicine and Thoracic Oncology, Klinikum Rheine - Mathias-Spital, Rheine, Germany. 28. Oncology Clinic, Policlinico SS. Annunziata, Chieti, Italy. 29. Asklepios Cancer Center Hamburg, Asklepios Klinikum Harburg, Hamburg, Harburg, Germany. 30. Department of Oncology at San Luigi Hospital, University of Torino, Orbassano (Torino), Italy. 31. Department of Surgery, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
Abstract
BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.
BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.