RTOG 0417: efficacy of bevacizumab in combination with definitive radiation therapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma

Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):101-5. doi: 10.1016/j.ijrobp.2013.10.022.


Purpose: Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS).

Methods and materials: Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method.

Results: 49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively.

Conclusion: In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical cancer showed efficacy results that are promising and may warrant further investigation.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab
  • Carcinoma, Adenosquamous / mortality
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Adenosquamous / therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy / methods*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Confidence Intervals
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / therapeutic use*
  • Treatment Failure
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Young Adult


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Cisplatin