Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial (original) (raw)
Related papers
Lancet, 2013
Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investi...
The Oncologist, 2019
Background Regorafenib at the standard intermittent dosing schedule proved effective in the GRID trial for refractory gastrointestinal stromal tumors (GISTs). However, this dosing schedule requires frequent dose reduction, and the progression of GISTs or tumor-related symptoms during the off-treatment period has also been noted in some patients. Therefore, we conducted this phase II trial to evaluate the efficacy and safety of regorafenib at a lower dose on a continuous dosing schedule. Methods Patients with measurable, metastatic, or recurrent GISTs who failed to respond to both imatinib and sunitinib were eligible for this study. Regorafenib 100 mg p.o. daily was administered continuously. The primary endpoint was disease control rate (DCR: complete response plus partial response [PR] plus stable disease [SD]) lasting for at least 12 weeks using RECIST version 1.1. Results The best response was PR in 2 (8%), SD in 16 (64%), and progressive disease in 6 (24%) patients. DCR lasting ...
Journal of Gastrointestinal Cancer, 2012
Purpose To compare characteristics of patients, the risk of recurrence, and mortality among adult patients with primary resectable gastrointestinal stromal tumor (GIST) receiving short-term (6-12 months) versus long-term (≥24 months) imatinib therapy. Methods Detailed information on primary resectable KITpositive GIST patients initiated on imatinib adjuvant therapy was retrospectively collected for short-and long-term imatinib patients from 318 US oncologists using an online data collection form. Patient characteristics were compared using Wilcoxon and Chi-square tests. Disease recurrence and mortality rates were compared using multivariate Cox proportional hazard models. Results Among the 406 short-term and 406 long-term imatinib patients, the median follow-up was 916 and 970 days, respectively. While patients generally had similar demographic characteristics, the short-term group had a higher prevalence of cardiovascular and ischemic heart diseases and patients in the long-term group had a higher presurgery risk profile. This finding was consistent with the main reason reported by oncologists for prescribing adjuvant imatinib over longer duration, i.e., patient risk profile. Disease recurrence [5.9 versus 1.2 %, (p<.001)] and mortality rates [7.1 % versus 2.0 %, (p<.001)] were higher in short-versus long-term patients. The adjusted risk of recurrence was 5.30 times (p<.001) higher, and mortality risk was 4.02 times (p<.001) higher in short-versus long-term patients. Conclusions Patient risk profile is an important factor in oncologists' decisions to prescribe adjuvant imatinib. Despite the higher risk profile observed in long-term patients, the long-term use of imatinib was associated with a reduction in long-term risk of disease recurrence and mortality. Keywords Gastrointestinal stromal tumors. GIST. KIT. KIT inhibitors. Imatinib. Soft tissue sarcomas. Sarcomas Background A gastrointestinal stromal tumor (GIST) is a type of softtissue sarcoma that usually develops in cells within the wall of the stomach or intestines. GISTs may result from the over-expression or activation of mutation in KIT (CD117) protein or platelet-derived growth factor receptor alpha which provides a stimulus for tumor cell proliferation [1, 2]. The incidence of a GIST is estimated to be approximately 3,000-6,000 cases per year in the US [3, 4]. Most common GISTs sites are stomach (60 %), jejunum and ileum (30 %), duodenum (5 %), and colorectum (<5 %) [5, 6]. Approximately 20 % to 25 % of gastric GISTs and 40 % to
Clinical Sarcoma Research, 2020
Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) pa...
BMC Cancer, 2012
Background: Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. Methods: We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2 nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST). Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis. A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98....
Adjuvant Imatinib for High-Risk GI Stromal Tumor: Analysis of a Randomized Trial
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015
Three years of adjuvant imatinib therapy are recommended for patients with GI stromal tumor (GIST) with high-risk features, according to survival findings in the Scandinavian Sarcoma Group XVIII/AIO (Arbeitsgemeinschaft Internistische Onkologie) trial. To investigate whether the survival benefits have persisted, we performed the second planned analysis of the trial. Eligible patients had macroscopically completely excised, KIT-positive GIST with a high risk of recurrence, as determined by using the modified National Institutes of Health criteria. After surgery, the patients were randomly assigned to receive imatinib for either 1 or 3 years. The primary objective was recurrence-free survival (RFS), and the secondary objectives included survival. A total of 400 patients were entered onto this open-label study between February 4, 2004, and September 29, 2008. During a median follow-up of 90 months, 171 recurrences and 69 deaths were detected. Patients assigned to the 3-year group had l...
Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients
Scientific reports, 2017
Regorafenib was approved as third-line therapy for advanced Gastrointestinal Stromal Tumour (GIST) at a starting dose of 160 mg daily 3 weeks on, 1 week off, based on improvement in progression free survival over placebo (4.8 vs. 0.9 months), but the response rate was low at 4.5%. Given the high toxicity rate in GIST patients, there is variability in the post-marketing dosing of regorafenib. We aimed to summarize our experience regarding prescribing patterns, efficacy and toxicity of regorafenib and determine the role of response assessment by Choi criteria in GIST patients. We included 28 patients who received regorafenib from our pharmacy. Baseline patient characteristics and treatment outcomes were recorded and an independent radiologist assessed response using Choi and RECIST. Seventy-nine percent of patients started at a 120 mg continuous daily dosing schedule, different from the standard intermittent dosing schedule. Grade 3/4 adverse events were experienced by 43% of patients...