Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Krishnansu Sujata Tewari ◽  
Michael Sill ◽  
Harry J. Long ◽  
Lois M. Ramondetta ◽  
Lisa Michelle Landrum ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Disease Progression ◽  
Interim Analysis ◽  
Gynecologic Oncology ◽  
Gynecologic Cancer ◽  
Single Agent ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Recurrent Cervical Cancer ◽  
Anti Vegf

3 Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab (B), a humanized anti-VEGF monoclonal antibody, has shown single-agent activity in pretreated recurrent disease. We aimed to evaluate B in chemotherapy (CTX)-naive recurrent/persistent/metastatic cervical cancer. Methods: Using a 2x2 factorial design, patients were randomly assigned to CTX with or without B 15 mg/kg. The CTX regimens included cisplatin 50 mg/m2 plus paclitaxel 135-175 mg/m2 and topotecan 0.75 mg/m2 d1-3 plus paclitaxel 175 mg/m2d1. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response. Overall survival (OS) was the primary endpoint with a reduction in the hazard of death by 30% using anti-VEGF therapy considered important (90% power, 1-sided alpha=2.5%). Final analysis was planned when 346 deaths were observed. Results: 452 patients were accrued from 4/6/09 to 1/3/12. The scheduled interim analysis occurred after 174 patients had died and showed that the topotecan-paclitaxel backbone was not superior to the cisplatin-paclitaxel backbone. A second interim analysis was conducted after 271 deaths. A total of 225 patients received CTX alone and 227 patients received CTX plus B. The randomized treatment groups were similar with regard to age, histology, performance status, previous platinum as a radiosensitizer, and recurrence, persistence, or advanced disease. The B-to-no-B hazard ratio (HR) of death was 0.71 (97.6% CI 0.54-0.95; 1-sided p=0.0035). Median survival was 17 m (CTX plus B) and 13.3 m (CTX alone). The RR were 48% (CTX plus B) and 36% (CTX alone) (p=0.0078). Treatment with B was associated with more grade 3-4 bleeding (5 vs 1%) thrombosis/embolism (9 vs 2%), and GI fistula (3 vs 0%). Conclusions: For the first time a targeted agent significantly improved OS in gynecologic cancer. The second interim analysis crossed the boundary for efficacy, warranting early release of this information. The nearly 4-month increase in median OS with the addition of B to CTX in women with recurrent cervical cancer is considered to be clinically significant. Clinical trial information: NCT00803062.

Factors predictive of response to cisplatin-based chemotherapy in stage IVB persistent or recurrent cervical carcinoma: A multivariate analysis of three Gynecologic Oncology Group trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5534-5534
Author(s):  
D. H. Moore ◽  
C. Tian ◽  
B. J. Monk ◽  
H. J. Long ◽  
G. Omura
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
African American ◽  
High Risk ◽  
Predictive Model ◽  
Single Agent ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Recurrent Cervical Cancer ◽  
Risk Of Death

5534 Purpose: A number of patients with advanced/recurrent cervical cancer do not respond to cisplatin-based chemotherapy. A pool analysis of three published phase III GOG studies was undertaken to identify the predictive factors and develop a model predictive of (non-) response to chemotherapy. Methods: The study population consisted of patients who received single-agent cisplatin or a cisplatin-containing combination in GOG protocols 110, 169 and 179. Prognostic variables (age, race, performance status, stage, histology, grade, disease site, prior chemotherapy—with primary radiation, time to recurrence, single-agent versus combination) were analyzed and multivariate analysis was conducted to identify factors independently predictive of response and survival. These analyses were used to establish a predictive model. Results: 816 patients were evaluable for response. In addition to single-agent treatment, multivariate analysis identified six factors (age, African-American, PS > 0, pelvic disease, prior radiosensitizer, recurrence ≤ one year) independently predictive of poor response. Those factors, but not age and African-American, were also independently associated with increased risk of death. 428 patients treated with a cisplatin- containing combination were classified into three risk groups based on the total number of risk factors (low risk: 0–1 factor; mid risk: 2–3 factors; high risk: 4–5 factors). Patients with 4–5 of risk factors were predicted to have a treatment response of only 13% (observed 10%), and median progression-free and overall survival of PFS of 2.8 months and 5.5 months, respectively. This subgroup of patients consist ∼14% of the target population in clinical practice. The predictive model was externally validated using GOG protocol 149 data that were not used for model development and further supported the predictive accuracy. Conclusions: High risk patients should be directed to non-cisplatin chemotherapy or investigational trials. No significant financial relationships to disclose.

Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3-3
Author(s):  
Krishnansu Sujata Tewari ◽  
Michael Sill ◽  
Harry J. Long ◽  
Lois M. Ramondetta ◽  
Lisa Michelle Landrum ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Randomized Trial ◽  
Annual Meeting ◽  
Gynecologic Oncology ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Daily News ◽  
Online Supplement ◽  
Final Text

3 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

Bevacizumab in the Treatment of Cervical Cancer – Current Evidence and Next Steps

2016 ◽  
Vol 12 (01) ◽  
pp. 32 ◽  
Author(s):  
Ana Oaknin ◽  
Victor Rodriguez-Freixinos ◽  
◽  
Keyword(s):  
Cervical Cancer ◽  
Gynecologic Oncology ◽  
Human Papilloma Virus Infection ◽  
Metastatic Carcinoma ◽  
Therapeutic Interventions ◽  
Phase Iii ◽  
Current Evidence ◽  
Gynecologic Oncology Group ◽  
Downstream Effects ◽  
Early Phase Clinical Trials

Despite the introduction of screening and, latterly, vaccination programmes in the developed world, cervical cancer remains a significant global health problem. For those diagnosed with advanced or recurrent disease, even within resource-rich communities, prognosis remains poor with an overall survival (OS) of just over 12 months. New therapeutic interventions are urgently required. Advances in our understanding of the mechanisms underlying tumour growth and the downstream effects of human papilloma virus infection identified angiogenesis as a rational target for therapeutic intervention in cervical cancer. Anti-angiogenic agents showed promising activity in early-phase clinical trials culminating in a randomised phase III study of the humanised monoclonal antibody to vascular endothelial growth factor, bevacizumab, in combination with chemotherapy. This pivotal study, the Gynecologic Oncology Group (GOG) protocol 240, met its primary endpoint, demonstrating a significant improvement in OS. Bevacizumab became the first targeted agent to be granted regulatory approval by the US Food and Drug Administration for use alongside chemotherapy in adults with persistent, recurrent or metastatic carcinoma of the cervix. This review outlines the rationale for targeting angiogenesis in cervical cancer focusing on the current indications for the use of bevacizumab in this disease and future directions.

scholarly journals Phase II Trial of Bevacizumab in the Treatment of Persistent or Recurrent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

2009 ◽  
Vol 27 (7) ◽  
pp. 1069-1074 ◽  
Author(s):  
Bradley J. Monk ◽  
Michael W. Sill ◽  
Robert A. Burger ◽  
Heidi J. Gray ◽  
Thomas E. Buekers ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Gynecologic Oncology ◽  
Gynecologic Oncology Group ◽  
Vascular Endothelial ◽  
Oncology Group ◽  
Recurrent Cervical Cancer ◽  
Endothelial Growth Factor

Purpose Vascular endothelial growth factor is a key promoter of tumor progression in cervical carcinoma. The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of bevacizumab, a recombinant humanized anti–vascular endothelial growth factor monoclonal antibody. Patients and Methods Eligible patients had recurrent cervical cancer, measurable disease, and GOG performance status ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and toxicity. Results Forty-six patients were enrolled (median age, 46 years); 38 patients (82.6%) received prior radiation as well as either one (n = 34, 73.9%) or two (n = 12, 26.1%) prior cytotoxic regimens for recurrent disease. Grade 3 or 4 adverse events at least possibly related to bevacizumab included hypertension (n = 7), thrombo-embolism (n = 5), GI (n = 4), anemia (n = 2), other cardiovascular (n = 2), vaginal bleeding (n = 1), neutropenia (n = 1), and fistula (n = 1). One grade 5 infection was observed. Eleven patients (23.9%; two-sided 90% CI, 14% to 37%) survived progression free for at least 6 months, and five patients (10.9%; two-sided 90% CI, 4% to 22%) had partial responses. The median response duration was 6.21 months (range, 2.83 to 8.28 months). The median PFS and overall survival times were 3.40 months (95% CI, 2.53 to 4.53 months) and 7.29 months (95% CI, 6.11 to 10.41 months), respectively. This compared favorably with historical phase II GOG trials in this setting. Conclusion Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer and merits phase III investigation.

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