Improved Survival with Bevacizumab in Advanced Cervical Cancer

By K. Tewari, M. Sill, H. Long, R. Penson, Helen Q. Huang, L. Ramondetta, L. Landrum, A. Oaknin, T. Reid, M. Leitao and 2 more. New England Journal of Medicine, 2014

1,261 citations recorded by the source corpus.

Background Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer. Methods Using a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important. Results Groups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan–paclitaxel was not superior to cisplatin–paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P = 0.004 in a one-sided test) and higher response rates (48% vs. 36%, P = 0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%). Conclusions The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.)

Subfields: Molecular Biology, Obstetrics and Gynecology, Oncology

View Paper: https://www.semanticscholar.org/paper/4caf00eeee96b8ca3779282e310663981e84271a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. A. Adamis
2. N. Ferrara
3. B. Chan
4. N. Colombo
5. B. Hughes
6. C. Marth
7. A. González-Martín
8. Rakesh K. Jain

In Obstetrics and Gynecology

1. N. Colombo
2. C. Marth
3. A. González-Martín

In Oncology

1. A. Adamis
2. N. Ferrara
3. Daniel Chen
4. R. Apte

Citations in the corpus

• Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. (2019, background): “007).(18) However, increased toxicity was observed with bevacizumab in this study, with a higher incidence of grade 3 or greater thromboembolism and GI and genitourinary fistulas.”
• Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. (2015, background): “Disrupting tumour blood supply and angiogenesis has been a enticing target for many years now (158) with some successes in other malignancies such as colorectal cancer (159), ovarian (160) and now cervical cancer (161).”
• Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. (2018, background): “lung [109, 110, 111], colon [109, 112, 113], esophagogastric [114, 115], breast [3, 24, 116], cervical [117],”
• Ten years of anti-vascular endothelial growth factor therapy (2016, background): “A Phase III study (GOG240) in patients with advanced cervical cancer found PFS and OS improvements when bevacizumab was combined with two different chemotherapy regimens 89 , leading to FDA approval in August 2014.”
• Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2017, background): “6% versus 1%), and these side-effects must be carefully monitored during treatment [49].”
• Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. (2016, positive): “Further improvements in survival could be achieved through the use of better IGBT techniques to further reduce local and pelvic recurrences in advanced stage disease [6,10,13,14], the use of paraaortic EBRT and the use of adjuvant chemotherapy and/or targeted drugs for patients at high risk for dist”