Preoperative chemoradiation and cetuximab for resectable, locally advanced esophageal cancer: Preliminary results of a prospective phase Ib/II trial.

e14571 Background: This prospective phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiation (CRT) in locally advanced esophageal cancer (LAEC). We hereby report its preliminary results. Methods: Patients (pts) with potentially resectable LAEC, defined as T2-4N0-1M0, T1-4N1M0 or T1-4N0-1M1A tumors, received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-FU 1000 mg/m2/day as a continuous infusion (CI), days 1–5, followed 4 weeks later by 50.4 Gy radiotherapy (RT) given concurrently with 2 cycles of cisplatin 75 mg/m2 and escalating doses of CI 5-FU, days 1–4 and 29-32. Pts received also 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose of 400 mg/m2, starting from the induction. The phase II part of the study started when the 5-FU dose during CRT was defined. Surgery was planned 6-8 weeks after CRT. Results: Thirty-six pts have been enrolled to date and 32 completed CRT. The median age was 65 years and 60% were males. The ratio of squamous/adeno histologies was 53%/47%. Pts had very advanced tumors: 95% T3-T4, 63% N1 and 28% M1A. In the absence of dose limiting toxicity, 31 pts received the phase II dose of 5-FU, defined as 1000 mg/m2/day. The most common grade >3 toxicities were leucopenia (51% of pts) and neutropenia (48%). There was one toxic death, due to neutropenic sepsis. Among the 27 operated pts, R0 resection was achieved in 24 (89%). There were 4 cases (15%) of postoperative mortality, due to infection (3 pts) or respiratory failure (1). Downstaging was noted in 83% of pts and pathological complete response (pCR) in 32%. Pts with squamous histology had a higher pCR rate (53% vs 7%, p=0.007). At the time of the analysis, 14 pts (40%) remain free of disease and the local control rate is 92%. Updated results will be presented at the meeting. Conclusions: Preliminary results from this prospective study suggest that the addition of cetuximab to standard CRT is safe. The R0, pCR and local control rates are encouraging. Squamous cell tumors may gain more benefit from the addition of cetuximab.