Publication
Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08)
Journal Paper/Review - Jun 1, 2018
Ruhstaller Thomas, Mingrone W, Montemurro M, Girschikofsky M, Schmidt S C, Bitzer M, Bedenne L, Brauchli P, Stahl M, Hess V, Mariette C, Hawle H, Thuss-Patience P, Hayoz S, Schacher S, Knorrenschild J R, Schnider A, Plasswilm L, Budach W, Eisterer W, Swiss Group for Clinical Cancer Research (SAKK), the German Esophageal Cancer Study Group, the Austrian ‘Arbeitsgemeinschaft Medikamentöse Tumortherapie’ (AGMT), and the Fédération Francophone de Cancérologie Digestive (FFCD)/Fédération de Recherche en Ch
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PubMed
Doi
Citation
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Journal
Publication Date
Issn Electronic
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Brief description/objective
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.