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
3879 - Efficacy of derazantinib (DZB) in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) expressing FGFR2-fusion or FGFR2 mutations/amplifications
Presenter: Michele Droz Dit Busset
Session: Poster Display session 2
Resources:
Abstract
4679 - It’s Not Only About Weight Loss: Tackling Pancreatic Cancer-Associated Cachexia
Presenter: Ana Leonor Matos
Session: Poster Display session 2
Resources:
Abstract
2276 - Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: a prospective observational study (PRELUDE study)
Presenter: Masafumi Ikeda
Session: Poster Display session 2
Resources:
Abstract
2773 - Post-hoc analyses of a subgroup of patients with advanced biliary tract cancer (BTC) who crossed over to treatment with etoposide toniribate (EDO-S7.1) in a randomized Phase II study
Presenter: Ulrich-Frank Pape
Session: Poster Display session 2
Resources:
Abstract
4479 - Capecitabine +Best supportive care (BSC) or Erlotinib +BSC has Overall survival (OS) benefit over BSC alone in unresectable/metastatic Gall bladder cancer(GBC) patients with ECOG PS-III. Results from a phase II Randomised controlled trial (RCT)
Presenter: Babita Kataria
Session: Poster Display session 2
Resources:
Abstract
4843 - FGFR2 fusions and its effect of patient (pt) outcomes in intrahepatic cholangiocarcinoma (iCCA)
Presenter: Daniel Almquist
Session: Poster Display session 2
Resources:
Abstract
2324 - The Clinical Outcomes of Systemic Chemotherapy in Patients with Unresectable or Metastatic Combined Hepatocellular-cholangiocarcinoma (HCC-CCA): Retrospective Study of 120 Patients
Presenter: Eojin Kim
Session: Poster Display session 2
Resources:
Abstract
3678 - High PD-L1 expression is associated with treatment response to pembrolizumab in patients with advanced biliary tract cancer.
Presenter: Gilhyang Kim
Session: Poster Display session 2
Resources:
Abstract
3901 - Genomic profiling in Chinese biliary tract cancer patients with PI3K/AKT/mTOR pathway and RAS gene mutations
Presenter: Jingyu Cao
Session: Poster Display session 2
Resources:
Abstract
4390 - Phase II trial of trifluridine/tipiracil (TAS-102) in patients with advanced refractory biliary tract cancer (BTC)
Presenter: Sakti Chakrabarti
Session: Poster Display session 2
Resources:
Abstract