Phase II Trial of Neoadjuvant Bevacizumab with Modified FOLFOX7 in Patients with Stage II and III Rectal Cancer

Abstract

LESSONS LEARNED: Neoadjuvant BEVmFOLFOX7 without radiation failed to meet the goal of pathological complete response rate; however, the low number of recurrence disease-free survival in this population, with predominantly stage III, is encouraging and worth further exploration. The racial distribution of the patient population, as well as a wait time of more than 4 weeks after last chemotherapy, may have contributed to the findings. BACKGROUND: Combination chemotherapy in lieu of radiation in rectal adenocarcinoma is under exploration in multiple trials. We evaluated the efficacy of neoadjuvant FOLFOX + bevacizumab in patients (pts) with clinical stage II and III disease. METHODS: Pts received 6 cycles of bevacizumab (5 mg/kg) and mFOLFOX7 (oxaliplatin 85 mg/m(2) , leucovorin 20 mg/m(2) , and 5-FU 2,400 mg/m(2) ). Surgical resection was performed 6-8 weeks after completion of treatment and upon confirmation of non-metastatic disease. We employed a Simon two-stage design and required 3 pathological complete responses (pCR) in the first 18 pts with a prespecified pCR rate of 25% before moving to the next stage. RESULTS: Seventeen pts enrolled; 65% stage III. Median age was 57 (35-79), 65% male, 47% Hispanic, 35% Caucasian, and 18% Asian. All pts but one completed 6 cycles of therapy. One pCR was observed (6%) and 11/17 (65%) had pathological down staging. One patient experienced systemic recurrence and remains on treatment. Probability of Disease Free Survival (DFS) at 5 years is 0.94 (SE: 0.06). CONCLUSION: The study failed to meet the required 3 pCRs in the first 18 pts. The DFS in this population is encouraging and supports the hypothesis that select pts with rectal cancer may be spared from radiation.