Abstract 3284
Background
Adding BEV to P + cisplatin/topotecan for aCC significantly improved overall survival (OS) and progression-free survival (PFS) in the phase 3 GOG240 trial. CECILIA (NCT02467907) evaluated BEV with a more widely used CP backbone.
Methods
The primary objective was to determine the safety of BEV + CP for aCC, defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula. Eligible patients (pts) had metastatic/recurrent/persistent CC not amenable to curative surgery and/or radiotherapy (RT). Pts with ongoing bladder/rectal involvement, prior cobalt RT, history of fistula/GI perforation, or bowel resection ≤6 wk or chemoRT ≤3 mo before first dose were excluded. Pts received BEV 15 mg/kg, P 175 mg/m2 and C AUC 5 q3w until disease progression (PD), unacceptable toxicity or consent withdrawal. If BEV, C or P was stopped for adverse events (AEs), the remaining drug(s) could be continued alone.
Results
From Jul 2015 to Dec 2016, 150 pts began treatment. Disease status at study entry was persistent in 20%, recurrent in 53% and metastatic at diagnosis in 27%; 71% had received prior RT (chemoRT in 58%) and 59% prior platinum. At data cutoff (31 Dec 2018), median follow-up was 27.8 mo. The most common reasons for stopping treatment were PD (39%) and AEs (34%). Median BEV duration was 6.7 (range <1–39) mo; 57% received BEV alone after stopping CP. 17 pts (11.3%, 95% CI 6.7–17.5%) had ≥1 perforation/fistula event: GI perforation/fistula in 4.7% (1.9–9.4%), GI-vaginal fistula in 4.0% (1.5–8.5%) and GU fistula in 4.7% (1.9–9.4%). All but 1 pt with fistula/GI perforation had received prior RT; several had ongoing radiation effects. The most common grade 3/4 AEs were neutropenia (21%), anaemia (19%) and hypertension (14%). 5 pts (3%) had fatal AEs. Objective response rate was 61% (95% CI 52–69%), including complete responses in 14%. Median PFS was 10.9 (95% CI 10.1–13.7) mo and median OS 25.0 (20.9–30.4) mo.
Conclusions
These results show that BEV can be combined with CP in the CECILIA study population. The fistula/GI perforation incidence is in line with GOG240 and efficacy results are encouraging.
Clinical trial identification
NCT02467907.
Editorial acknowledgement
Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche.
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
F. Hoffmann-La Roche.
Disclosure
A. Redondo: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche Farma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Research grant / Funding (institution): Eisai. N. Colombo: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: BIOCAD; Advisory / Consultancy: Takeda; Advisory / Consultancy: Lilly; Non-remunerated activity/ies, ESMO Clinical Guidelines: ESMO; Non-remunerated activity/ies, Scientific Committee Chair: ACTO Onlus. L.M. Dreosti: Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Merck. M. McCormack: Honoraria (self): AstraZeneca; Honoraria (self): Roche. A. Nogueira Rodrigues: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD. M. Donica: Shareholder / Stockholder / Stock options: Novartis; Full / Part-time employment: Roche. B. Ulker: Full / Part-time employment: F. Hoffmann-La Roche AG. A. González Martín: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Non-remunerated activity/ies, PI of PRIMA: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy: MSD; Advisory / Consultancy: Genmad. All other authors have declared no conflicts of interest. Scientific clarification
Resources from the same session
3191 - The efficacy and safety of lenvatinib in patients who did not meet the inclusion criteria of the phase 3 trial (REFLECT trial) and those with BCLC Stage B hepatocellular carcinoma - A nationwide multicenter study in Japan-
Presenter: Azusa Sakamoto
Session: Poster Display session 2
Resources:
Abstract
1529 - Prognostic and predictive value of baseline alpha-fetoprotein (AFP) in patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab from two phase 3 studies (REACH, REACH-2)
Presenter: Andrew Zhu
Session: Poster Display session 2
Resources:
Abstract
2767 - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study
Presenter: Nicholas Freemantle
Session: Poster Display session 2
Resources:
Abstract
2150 - Alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (HCC) in the phase 3 RESORCE trial
Presenter: Jordi Bruix
Session: Poster Display session 2
Resources:
Abstract
3437 - Phase I/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis
Presenter: Marc Pracht
Session: Poster Display session 2
Resources:
Abstract
1758 - Efficacy and safety of ramucirumab (RAM) for advanced hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) following first-line sorafenib across age subgroups in two global phase 3 trials (REACH and REACH-2)
Presenter: Masatoshi Kudo
Session: Poster Display session 2
Resources:
Abstract
1192 - Ramucirumab in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): An exposure–response analysis
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1600 - Outcomes of Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab: The Mount Sinai Hospital Experience.
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2364 - Pembrolizumab vs Chemotherapy in Patients With Advanced/Metastatic Adenocarcinoma (AC) or Squamous Cell Carcinoma (SCC) of the Esophagus as Second-Line Therapy: Analysis of the Chinese Subgroup in KEYNOTE-181
Presenter: Jia Chen
Session: Poster Display session 2
Resources:
Abstract
1933 - A national comparative effectiveness study to assess definitive chemoradiation regimens in proximal oesophageal squamous cell cancer
Presenter: Judith de Vos-Geelen
Session: Poster Display session 2
Resources:
Abstract