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Abstract
Introduction/Background In the phase III GOG240 trial, combining bevacizumab with paclitaxel and cisplatin/topotecan for advanced cervical cancer significantly improved overall and progression-free survival. The single-arm phase II CECILIA study (NCT02467907) evaluated bevacizumab with a more widely used chemotherapy backbone.
Methodology The primary objective was to determine the safety of bevacizumab/carboplatin/paclitaxel for advanced cervical cancer, defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula. Eligible patients had metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, history of fistula/GI perforation, or bowel resection ≤6 weeks or chemoradiation ≤3 months before starting bevacizumab were excluded. Patients received bevacizumab 15 mg/kg, paclitaxel 175 mg/m2 and carboplatin AUC5 q3w until disease progression, unacceptable toxicity or consent withdrawal. If any drug was stopped for toxicity, the remaining drug(s) could be continued alone.
Results Between July 2015 and December 2016, 150 patients began treatment. Baseline characteristics at study entry were: 20%/53%/27% with persistent/recurrent/de novo metastatic disease; 71%/58%/59% with prior radiotherapy/chemoradiation/platinum. Median treatment duration was 6.7 (range <1–39) months for bevacizumab and 3.9 (range 0–14.6) months for chemotherapy; 57% of patients received single-agent bevacizumab after discontinuing chemotherapy. Table 1 summarises primary endpoint results. In 17 patients with fistula/perforation events, median time to onset was 3.8 (range 0.3–12.4) months. Grade 3/4 adverse events occurred in 73% of patients, most commonly neutropenia/neutrophil count decreased (25%), anaemia (19%) and hypertension (14%). Grade 5 adverse events occurred in 3%. Figure 1 shows progression-free and overall survival. The objective response rate was 61% (95% CI 52–69%), including complete responses in 14% (9–21%).
Summary of primary endpoint results
Progression-free and overall survival
Conclusion Bevacizumab can be combined with carboplatin/paclitaxel chemotherapy in the cervical cancer population treated in CECILIA. The fistula/GI perforation incidence is in line with GOG240. Efficacy results are encouraging.
Disclosure Nicoletta Colombo:advisor/consultant for Roche, PharmaMar, AstraZeneca, Tesaro, Clovis, Pfizer, MSD, BIOCAD, Takeda, Lilly; travel/accommodation expenses from Roche, PharmaMar, Tesaro. Lydia Dreosti: honoraria for advisory/consultancy roles from Eli Lilly, MSD; travel/accommodation expenses from Janssen, Merck. Mary McCormack: honoraria from AstraZeneca, Roche. Angélica Nogueira-Rodrigues: honoraria for advisory boards/consultancy from Roche, AstraZeneca, MSD; research funding to institution from Roche, MSD. Giovanni Scambia, Andrzej Roszak: no conflict of interest. Margarita Donica: employee of F Hoffmann-La Roche; shares in Novartis. Bulent Ulker: contracted to work on behalf of F Hoffmann-La Roche. Antonio González-Martín: advisory boards for Roche, AstraZeneca, Tesaro, Clovis, Pfizer, ImmunoGen, PharmaMar, MSD, Genmad; speaker bureau for Roche, PharmaMar, Tesaro, AstraZeneca; research funding to institution from Roche, Tesaro. Andrés Redondo: honoraria from AstraZeneca, Roche Farma, Tesaro, Clovis, Pharmamar, Lilly, Eisai; advisory boards for AstraZeneca, Roche Farma, Tesaro, Clovis, Pharmamar, Lilly; travel/accommodation from AstraZeneca, Tesaro, PharmaMar, Roche Farma; research funding to institution from Eisai, PharmaMar, Roche Farma.