title: NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer.
abstract: BACKGROUND
  The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.
  
  
  METHODS
  Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).
  
  
  RESULTS
  A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months.
  
  
  CONCLUSIONS
  Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Akila N
authors.initials: AN
authors.lastname: Viswanathan
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.affiliation: Carolinas Healthcare System NorthEast, Levine Cancer Institute, Concord, North Carolina.
authors.forename: Brigitte E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Anuja
authors.initials: A
authors.lastname: Jhingran
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Portelance
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Walter R
authors.initials: WR
authors.lastname: Bosch
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Horowitz
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Erickson
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.affiliation: Loyola University, Chicago, Illinois.
authors.forename: William
authors.initials: W
authors.lastname: Small
authors.affiliation: University of Utah Health Science Center, Salt Lake City, Utah.
authors.forename: David K
authors.initials: DK
authors.lastname: Gaffney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011184:Postoperative Period; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D000068258:Bevacizumab; D017239:Paclitaxel; D002945:Cisplatin
keywords: bevacizumab; chemotherapy; endometrial cancer; intensity-modulated radiotherapy (IMRT); radiation
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