Abstract 2011
Background
Advanced esophagogastric cancer (EGC) has a dismal prognosis of less than one year. Survival has improved with second line therapies, such as the combination of the angiogenesis inhibitor Ramucirumab and Paclitaxel (PTX). Monotherapy with Regorafenib (Reg), a multikinase inhibitor of angiogenic, stromal, and oncogenic kinases, demonstrated an improved progression-free survival (PFS) in advanced gastric cancer. In the REPEAT trial, we assessed the tolerability of Reg in combination with PTX for beyond first-line treatment of patients (pts) with advanced EGC.
Methods
Pts with metastatic EGC who progressed after first-line treatment, received PTX 80 mg/m2 i.v. on day 1, 8, and 15 of a 28-day cycle, and 120 mg Reg on day 1-21 of a 28-day cycle, as determined in phase Ib. Toxicity was assessed using CTCAE version 4, and Kaplan-Meier estimates of overall survival (OS) and PFS were done. In tumour biopsies, the effect of Reg on PTX uptake and Reg targets will be assessed, and the effect of Reg on PTX pharmacokinetics will be evaluated.
Results
Reg 120 mg on day 1-21 combined with PTX was well tolerated in the Ib phase (N = 14), and 33 pts were enrolled in the expansion cohort (total 47 pts, 81% received 120 mg). The majority of pts received treatment as second-line (60%); the remainder as third line or beyond. Most common grade 1/2 toxicities included fatigue (11%), peripheral sensory neuropathy (9%), diarrhea (5%), and alopecia (5%). Hypertension (10%), diarrhea (7%), and peripheral sensory neuropathy (5%) were the most common grade 3/4 toxicities. Median number of cycles was 4 (IQR 2-6), with 5 pts still on treatment (median follow-up 6.9 months). Best responses achieved were partial response (26%), stable disease (51%), and progressive disease (15%), with 4 patients not evaluable. Reasons for treatment discontinuation were progression (n = 36), toxicity (n = 5), or patient decision (n = 1). Median PFS and median OS were 4.1 months and 7.8 months, respectively.
Conclusions
The combined treatment of Reg with PTX is tolerable and shows promising effects on survival in beyond first-line treatment of advanced EGC. PK analyses and biomarker analyses on biopsies of metastatic lesions are ongoing.
Clinical trial identification
2014-005433-31 Release date: 10th December 2014.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bayer.
Disclosure
J. de Vos-Geelen: Non-remunerated activity/ies: BTG; Research grant / Funding (institution), Non-remunerated activity/ies, Outside submitted work: Servier; Advisory / Consultancy: Shire. M. van Oijen: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nordic. M. Bijlsma: Research grant / Funding (institution), Outside submitted work: Celgene; Research grant / Funding (institution), Outside submitted work: Servier. H.W.M. van Laarhoven: Honoraria (self), Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy, Research grant / Funding (institution): Nordic Group; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Bayer Schering Pharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Philips Healthcare; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.
Resources from the same session
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
1025 - Liver metastases (LM) from intrahepatic cholangiocarcinoma (iCCA): Outcomes from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry and implications on current American Joint Committee on Cancer (AJCC) staging.
Presenter: Angela Lamarca
Session: Poster Display session 2
Resources:
Abstract
5813 - Is MGMT methylation a new therapeutic target for Biliary Tract Cancer?
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5839 - Biliary Tract Cancers in Portuguese families with BRCA gene mutation: a retrospective study.
Presenter: Patricia Pereira
Session: Poster Display session 2
Resources:
Abstract
4338 - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: a post-hoc analysis of the SARAH trial
Presenter: Daniel Palmer
Session: Poster Display session 2
Resources:
Abstract
1700 - Second-line chemotherapy (SLC) in Patients with Advanced Biliary tract and Gallbladder Cancers (ABGC) Prolongs Survival: A Retrospective Population-based Cohort Study
Presenter: Adnan Zaidi
Session: Poster Display session 2
Resources:
Abstract
5562 - Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted dosimetry in the SARAH trial
Presenter: Neil Hawkins
Session: Poster Display session 2
Resources:
Abstract
1838 - Multicenter phase II trial of axitinib monotherapy for advanced biliary tract cancer refractory to gemcitabine-based chemotherapy
Presenter: Naohiro Okano
Session: Poster Display session 2
Resources:
Abstract
3641 - Soluble Programmed Death-ligand 1 indicate poor prognosis in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization
Presenter: Xiaolu Ma
Session: Poster Display session 2
Resources:
Abstract
2733 - The Prognostic Nutritional Index (PNI) is an independent predictor of survival in advanced biliary cancers (ABC) receiving first-line chemotherapy (1L).
Presenter: Francesco Caputo
Session: Poster Display session 2
Resources:
Abstract