Andres Redondo1, Nicoletta Colombo2, Mary McCormack3, Lydia Dreosti4, Angelica Nogueira-Rodrigues5, Giovanni Scambia6, Domenica Lorusso7, Florence Joly8, Michael Schenker9, Paul Ruff10, Maria Estevez-Diz11, Natsumi Irahara12, Margarita Donica13, Antonio Gonzalez-Martín14. 1. Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. Electronic address: andres.redondos@uam.es. 2. European Institute of Oncology, IRCCS, University of Milan-Bicocca, Milan, Italy. 3. Department of Oncology, University College London Hospitals, London, UK. 4. Department of Medical Oncology, University of Pretoria, Pretoria, South Africa. 5. Medical Oncology Department, Federal University of Minas Gerais Brazil and Brazilian Group of Gynecologic Oncology, Belo Horizonte, Brazil. 6. Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy. 7. Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy; Istituto Nazionale Tumori IRCCS, Milan, Italy. 8. Centre FranÇois Baclesse, caen, France. 9. Centrul de Oncologie Sf Nectarie Craiova, Craiova, Romania. 10. Division of Medical Oncology, University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa. 11. Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 12. Product Development Medical Affairs, F Hoffmann-La Roche Ltd, Basel, Switzerland. 13. Pharma Development Biostatistics Oncology, F Hoffmann-La Roche Ltd, Basel, Switzerland. 14. Clínica Universidad de Navarra, Madrid, Spain.
Abstract
OBJECTIVE: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone. METHODS: Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. RESULTS: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months. CONCLUSIONS: Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging. TRIAL REGISTRATION NUMBER: NCT02467907 (ClinicalTrials.gov).
OBJECTIVE: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone. METHODS:Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. RESULTS: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months. CONCLUSIONS:Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging. TRIAL REGISTRATION NUMBER: NCT02467907 (ClinicalTrials.gov).
Authors: Michael J Birrer; Keiichi Fujiwara; Ana Oaknin; Leslie Randall; Laureen S Ojalvo; Christian Valencia; Isabelle Ray-Coquard Journal: Front Oncol Date: 2022-02-23 Impact factor: 6.244