P-068 Cetuximab in addition to oxaliplatin, fluorouracil and radiotherapy for patients with esophageal cancer treated without surgery

Abstract

Introduction: This multicenter phase II trial investigated the addition of cetuximab to chemoradiotherapy in patients with esophageal cancer not suitable for surgery. Aims were to evaluate progression‐free survival at 1 year, overall survival and toxicity. Methods: Patients with biopsy‐proven squamous cell or adenocarcinoma in the esophagus or gastro‐esophageal junction, T2‐4, N0‐3, M0 and ECOG performance status 0‐2 were planned to receive three 21‐day cycles of fluorouracil 750 mg/m2 D1‐5 and oxaliplatin D1 (cycle 1: 130mg/m2, cycle 2‐3: 85 mg/m2). Radiation was administered to 50 Gy in 2 Gy/fraction, 5 days a week concurrent with cycle 2 and 3 and weekly cetuximab (loading dose 400mg/m2 and then 250 mg/m2). Merck Serono contributed with an unrestricted grant and has not been involved in study design or interpretation of results. Clinical trial information: NCT02636088. Results: Fifty‐two patients were included. The study was closed prematurely when results from SCOPE‐1 and RTOG 0436 showed no benefit from the addition of cetuximab to chemoradiotherapy in esophageal cancer. Median age: 66,5, range 34‐76. ECOG performance status (%) 0:1:2:not known 42:42:11:4. Morphology (%) squamous cell carcinoma:adenocarcinoma 77:19 (1 patient had both). Tumor stage (%), II:III 27:73. Tumor location (%) proximal:mid:distal:cardia 53:23:23:4 (2 patients had 2 locations). Ten did not receive any treatment as planned due to: patient's request (3), death (3), rapidly progressive disease (1), care‐givers request (1), non‐compliance (1), on treatment when study closed (1). Of those 6 were excluded from the study in accordance with the study protocol. Of the remaining 42, 38 received all 3 cycles of chemotherapy, 39 received radiotherapy as planned (2 received a higher dose), 26 received all 6 infusions of cetuximab (6 did not receive 1 of the doses and 5 did not receive 2 of the doses due to adverse events, 4 got severe allergic reactions and received less than 1 infusion, 1 refused cetuximab. Patients experiencing treatment related toxicity (%) grade 3:4 46:11. Most common grade 3/4 toxicities were (%) dysphagia: infection:anorexia:rash:esophagitis:allergic reaction 15:13:11:9:9:9. 5 patients (11%) died within 3 months from registration of which 2 were toxic deaths from drugs (interstitial lung disease and gastro‐intestinal necrosis). Failure‐free survival at 1 year: 32,6% (95% CI 19,1‐46,2). Median survival 12,5 months (95% CI 5,9‐19,1). Three‐year overall survival: 26,1% (95% CI 15,6‐40,3). Conclusion: Treatment was well tolerated and cetuximab did not seem to affect treatment intensity in this study in the same negative way as it did in SCOPE‐1 which might be explained by a different chemotherapy backbone. Mortality was high which is to be expected in this group of patients. Our results are similar to previously reported data from definitive chemoradiotherapy for esophageal cancer with or without the addition of cetuximab.