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

Abstract

Lessons learned: Neoadjuvant bevacizumab with modified FOLFOX7 without radiation failed to meet the goal of pathological complete response rate; however, the low number of recurrence and 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 six cycles of bevacizumab (5 mg/kg) and modified FOLFOX7 (oxaliplatin 85 mg/m2 , leucovorin 20 mg/m2 , and fluorouracil [5-FU] 2,400 mg/m2 ). Surgical resection was performed 6-8 weeks after completion of treatment and upon confirmation of nonmetastatic disease. We employed a Simon two-stage design and required three 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% at stage III. Median age was 57 (35-79), 65% were male, 47% were Hispanic, 35% were white, and 18% were Asian. All pts but one completed six cycles of therapy. One pCR was observed (6%), and 11 of 17 (65%) pts had pathological downstaging. 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 three 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.

Trial registration: ClinicalTrials.gov NCT01871571.

© AlphaMed Press; the data published online to support this summary are the property of the authors.

Figures

Figure 1

Overall and disease‐free survival. Overall (red) and disease‐free (blue) survival with median follow‐up of 44.8 (27.4–63.9) months.