The addition of cetuximab to preoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rate of long term survival: Mature results from a prospective phase Ib/II trial

Aim: This phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiotherapy (CRT) in locally advanced esophageal cancer (LAEC). Methods: Patients (pts) with resectable LAEC (T _2-3 N _0-1 M ₀ , T _1-3 N ₁ M ₀ or T _1-3 N _0-1 M _1A) received an induction cycle of cisplatin 100 mg/m ² , day 1, and 5-fluorouracil (5-FU) 1000 mg/m ² /day, days 1–5, followed 4 weeks later by radiotherapy, 50.4 Gy, given with 2 cycles of cisplatin 75 mg/m ² and escalating doses of 5-FU, days 1–4 and 29–32. Pts received 10 weekly infusions of cetuximab, 250 mg/m ² , with a loading dose, 400 mg/m ² . Surgery was planned 6–8 weeks after CRT. Results: 64 pts were treated and 60 completed CRT. Median age was 65 years and 66% were males. Adenocarcinoma/squamous ratio was 61%/39%. Tumors were advanced: 95% T ₃ and 67% N ₁ . Grade ≥3 toxicities occurred in 72%, with two (3%) toxic deaths. The 5-FU maximal tolerated dose (MTD) was 1000 mg/m ² /day. Clinical complete response rate was 33%. Of the 55 operated pts, R0 resection was achieved in 51 (93%) and pathological complete response (pCR) in 18 (33%), with 8 (14%) postoperative deaths. The 5-year survival rate for all pts was 38%. Pts with squamous histology had higher pCR (55% vs 20%, p = 0.015), local control (96% vs. 74%, p < 0.001) and 5-year survival (58% vs 25%, p = 0.011) rates. Conclusions: This study suggests that the addition of cetuximab to standard preoperative CRT is feasible. R0, pCR and local control rates are encouraging. Pts with squamous cell tumors benefited more from the addition of cetuximab.