T Ruhstaller1, P Thuss-Patience2, S Hayoz3, S Schacher4, J R Knorrenschild5, A Schnider6, L Plasswilm7, W Budach8, W Eisterer9, H Hawle3, C Mariette10, V Hess11, W Mingrone12, M Montemurro13, M Girschikofsky14, S C Schmidt2, M Bitzer15, L Bedenne16, P Brauchli3, M Stahl17. 1. Cantonal Hospital of St. Gallen, St. Gallen, Switzerland. Electronic address: thomas.ruhstaller@kssg.ch. 2. Charité - University Medicine, Berlin, Germany. 3. SAKK Coordinating Center, Berne, Switzerland. 4. Cantonal Hospital of Winterthur, Winterthur, Switzerland. 5. University Hospital of Giessen and Marburg, Germany. 6. City Hospital Triemli, Zürich, Switzerland. 7. Cantonal Hospital of St. Gallen, St. Gallen, Switzerland; University of Berne, Berne, Switzerland. 8. University Hospital Düsseldorf, Düsseldorf, Germany. 9. Medical University of Innsbruck, Innsbruck, Austria. 10. Hôpital Universitaire C. Huriez, Lille, France. 11. University Hospital of Basel, Basel, Switzerland. 12. Cantonal Hospital of Olten, Olten, Switzerland. 13. University Hospital of Lausanne, Lausanne, Switzerland. 14. Ordensklinikum Linz Elisabethinen, Linz, Austria. 15. University Hospital of Tübingen, Tübingen, Germany. 16. Hospital Center Regional University of Dijon, Dijon, France. 17. Kliniken Essen-Mitte, Essen, Germany.
Abstract
Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.
RCT Entities:
Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.
Authors: Michael K Gibson; Paul Catalano; Lawrence R Kleinberg; Charles A Staley; Elizabeth A Montgomery; Antonio Jimeno; Wei Frank Song; Mary F Mulcahy; Lawrence P Leichman; Al B Benson Journal: Oncologist Date: 2019-06-21
Authors: Karsten Kleo; Vladimir M Jovanovic; Alexander Arndold; Annika Lehmann; Hedwig Lammert; Erika Berg; Hannah Harloff; Christoph Treese; Michael Hummel; Severin Daum Journal: J Cancer Res Clin Oncol Date: 2022-03-05 Impact factor: 4.553