Chemoradiation with or without nimotuzumab in locally advanced esophageal cancer (LAEC): A randomized phase II study (NICE trial).

4078 Background: Chemoradiation is the standard therapy for patients (pts) with inoperable LAEC. We sought to assess the safety and activity of chemoradiation combined with nimotuzumab, a humanized antibody against the epidermal growth factor receptor, in LAEC. Methods: We randomized pts with inoperable LAEC, previously untreated, and with no distant metastases 1:1 to chemoradiation (cisplatin 75 mg/m2 D1, and 5-FU 1 g/m2/d CI D1-4, both for four 28-day cycles, combined with external-beam radiation 50.4 Gy) or the same chemoradiation plus nimotuzumab 200 mg IV, once weekly for 26 wks. The primary endpoint was endoscopic complete response (eCR, defined as absence of elevated, vegetative or exophytic lesions), whereas combined eCR/pathologic CR (pCR), overall survival (OS), quality of life and safety were secondary endpoints. Results: We enrolled 107 pts, 82% male, mean age 59 y. 100 pts (93%) had squamous cell carcinoma (SCC); performance status (ECOG-PS) was 0/1 in 34%/60% of cases. The relative dose intensity of chemotherapy and radiotherapy was nearly identical in both arms, and the median number of nimotuzumab doses was 24. We performed post-treatment endoscopy in 67 pts, in 60 of whom with biopsy. In the ITT population, eCR rates with vs. without nimotuzumab were 47.2% vs. 33.3% (p=0.17), whereas combined eCR/pCR rates were 62.3% vs. 37.0% (p=0.02). In a median follow-up of 14.7 mo., the hazard ratio (HR) for OS was 0.68 (95%CI 0.44-1.07; p=0.09), with a median OS of 15.9 vs. 11.5 months, respectively. In an unplanned subgroup analyses, the HR for OS in pts with ECOG-PS 0 was 0.32 (95%CI 0.12-0.85; p=0.02). We found no significant differences in quality of life between arms. Toxicity was manageable in both arms, with no significant differences in adverse events or serious adverse events. Conclusions: Combined chemoradiation and nimotuzumab is safe in pts with LAEC, and appears to increase the combined eCR/pCR rate and to impact favorably on OS. This is a promising regimen in pts with locally advanced esophageal SCC, and a phase III trial is under consideration. Clinical trial information: NCT01249352.