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
2840 - Effects of Aerobic and Resistance Exercise on Android:Gynoid Fat Ratio in Breast Cancer Survivors
Presenter: Christina Dieli-Conwright
Session: Poster Display session 2
Resources:
Abstract
869 - Impact of Education for Breast self examination in Rural Indian Women on Early Detection - results of POC study
Presenter: Sneha Parchuri
Session: Poster Display session 2
Resources:
Abstract
1951 - Breast cancer incidence and survival in renal transplant patients: 35-year experience
Presenter: Michalis Kontos
Session: Poster Display session 2
Resources:
Abstract
2017 - The changing landscape of breast cancer incidence after treatment for Hodgkin’s disease
Presenter: Amelia Benjamin
Session: Poster Display session 2
Resources:
Abstract
1780 - Number of deliveries as a prognostic factor in different breast cancer subtypes
Presenter: Anniina Jääskeläinen
Session: Poster Display session 2
Resources:
Abstract
4650 - Effects of supervised and adapted exercise program in the quality of life and strength of breast cancer survivors: MAMA MOVE Gaia trial
Presenter: Ana Joaquim
Session: Poster Display session 2
Resources:
Abstract
4962 - Study On the Socioeconomic and Clinical Factors Affecting the Proportion of Breast Conserving Surgery in Chinese Women Breast Cancer
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract
5451 - Clinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program?
Presenter: Marco Giavarra
Session: Poster Display session 2
Resources:
Abstract
888 - The value of genetic counselling in breast cancer genetic testing and clinical management
Presenter: Vicki Kiesel
Session: Poster Display session 2
Resources:
Abstract
4005 - Elderly patients in the Japanese Breast Cancer Registry
Presenter: Masataka Sawaki
Session: Poster Display session 2
Resources:
Abstract