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
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract
4581 - Timing to achieve complete response (CR) after definitive chemoradiotherapy (ChRT) in patients with squamous cell carcinoma of the anal (SCCAC) with and without HIV infection: a multicenter retrospective study
Presenter: Marcos Camandaroba
Session: Poster Display session 2
Resources:
Abstract
1712 - Planned organ preservation for T2 T3 M0 rectal adenocarcinoma. A possible option using chemoradiotherapy (CRT) and Contact X-ray Brachytherapy (CXB). A French multicenter study.
Presenter: Jean-Pierre Gérard
Session: Poster Display session 2
Resources:
Abstract
4639 - A Phase 1b Study of E7046 (AN0025) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Rectal Cancer
Presenter: Lucjan Wyrwicz
Session: Poster Display session 2
Resources:
Abstract
2310 - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: a propensity score analysis
Presenter: Ahrong Ham
Session: Poster Display session 2
Resources:
Abstract
2747 - Neoadjuvant chemoradiotherapy with/without lateral lymph node dissection for low rectal cancer: Which patients can benefit?
Presenter: Daisuke Nishizaki
Session: Poster Display session 2
Resources:
Abstract
2877 - The impact of completeness of chemotherapy on the efficacy of irinotecan in the preoperative chemoradiotherapy of locally advanced rectal cancer.
Presenter: Jingwen Wang
Session: Poster Display session 2
Resources:
Abstract
3050 - Feasibility of robot-assisted surgery in elderly patients with rectal cancer
Presenter: Wei-Chih Su
Session: Poster Display session 2
Resources:
Abstract
4109 - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: a case-control non-inferiority trial
Presenter: Valerii Ivanov
Session: Poster Display session 2
Resources:
Abstract
4813 - Differential of the nutritional index before and after neoadjuvant chemoradiotherapy as a prognostic factor of recurrence in patients with locally advanced adenocarcinoma of the rectum
Presenter: Leslie Navia-Ortuño
Session: Poster Display session 2
Resources:
Abstract