A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix: An NRG Oncology/Gynecologic Oncology Group study

• Published in: Gynecologic oncology 2017-09, Vol.146 (3), p.554-559
• Main Authors: Chan, John K., Deng, Wei, Higgins, Robert V., Tewari, Krishnansu S., Bonebrake, Albert J., Hicks, Michael, Gaillard, Stephanie, Ramirez, Pedro T., Chafe, Weldon, Monk, Bradley J., Aghajanian, Carol
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alanine - adverse effects; Alanine - analogs & derivatives; Alanine - supply & distribution; Alanine - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - supply & distribution; Antineoplastic Agents - therapeutic use; Brivanib; Carcinoma - drug therapy; Carcinoma - therapy; Disease Progression; Disease-Free Survival; Early Termination of Clinical Trials; Female; Humans; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - therapy; Recurrent cervical carcinoma; Response Evaluation Criteria in Solid Tumors; Retreatment; Survival Rate; Triazines - adverse effects; Triazines - supply & distribution; Triazines - therapeutic use; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - therapy
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2017.05.033

Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response. Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1–20). Seven (25%) patients had PFS >6months (90% CI: 7.3%–33.9%). Two (7%) (90% CI: 1.3%–20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1–4.4). The median overall survival was 7.9months (90% CI: 6.1–11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension. Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability. •In this phase II trial, brivanib was well tolerated and had sufficient activity.•Of 28 patients, 7% had partial response and 43% had stable disease•Common grade 3 adverse events were hypertension, anemia, hyponatremia, and nausea.