Jane Chang

Meta-analysis for the association between overall survival and progression-free survival in gastrointestinal stromal tumor

Purpose: Gastrointestinal stromal tumor (GIST) is a relatively rare tumor that is treated with targeted therapies in advanced stages. Randomized clinical trials (RCT) often require long follow-up and large sample sizes to evaluate overall survival (OS), the gold-standard measure of treatment efficacy. However, changes in therapy following disease progression may complicate survival assessments. Establishing surrogate endpoints may facilitate the drug approval and availability of new efficacious treatments; however, no published studies have investigated this topic in unresectable and/or metastatic GIST. Experimental Design: A systematic literature review identified 14 RCTs and five observational studies of sufficient methodologic quality published between January 1995 and December 2013 (29 treatment arms; 2,189 patients). Weighted linear regression was used to evaluate the relation between median OS and median progression-free survival (PFS) for all arms combined and stratified by treatment line, treatment type, and quality score. Results: Median OS and PFS were positively related with a correlation of 0.91. The association was still moderate (correlation 0.72) after eliminating four influential data points. In stratified analyses, correlation of OS and PFS was greater in later lines of therapy (first line = 0.52; second line = 0.80; third- and later-line = 0.70) and imatinib showed a stronger association (0.91) than other evaluated treatments (−0.26 to 0.69). Conclusion: This analysis identified a strong relationship between median OS and PFS, especially in later lines of therapy. Findings suggest that PFS could serve as a surrogate marker for OS; however, analyses of patient-level data are needed to establish its validity in GIST. Clin Cancer Res; 21(2); 295–302. ©2014 AACR.

Cost-Effectiveness Analysis of Regorafenib for Gastrointestinal Stromal Tumour (GIST) in Germany

BackgroundNo study has compared the cost-effectiveness of active treatment options for unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. The aim of this study was to estimate the cost-effectiveness of regorafenib compared to imatinib rechallenge in this setting in Germany.MethodsHazard ratios for progression-free (PFS) and overall survival (OS) with regorafenib versus imatinib rechallenge were estimated by indirect comparison. A state distribution model was used to simulate progression, mortality and treatment costs over a lifetime horizon. Drug acquisition costs and utilities were derived from clinical trial data and published literature; non-drug costs were not included. The outcomes measured were treatment costs, life-years (LYs) and quality-adjusted life-years (QALYs).ResultsThe indirect comparison suggested that median PFS and OS were longer with regorafenib compared to imatinib but results were not statistically significant. Regorafenib versus imatinib rechallenge was estimated to have hazard ratios of 0.58 (95% CI 0.31–1.11) for PFS and 0.77 (95% CI 0.34–1.77) for OS, with substantial uncertainty due to the rarity of the disease and small number of patients within the trials. Regorafenib treatment per patient over a lifetime horizon provided an additional 0.61 LYs and 0.42 QALYs over imatinib rechallenge, with additional direct drug costs of €8,773. The incremental cost-effectiveness ratio was €21,127 per QALY gained. At a cost-effectiveness threshold of €50,000 per QALY, regorafenib had a 67% probability of being cost-effective.ConclusionBased on the currently available clinical data, this analysis suggests that regorafenib is cost-effective compared with imatinib rechallenge in Germany.

Economic burden of common adverse events (AEs) associated with metastatic colorectal cancer (mCRC) treatment in the United States (US).

21 Background: Treatments for mCRC have distinct safety and tolerability profiles. Common AEs associated with mCRC treatments may compromise the course of treatment, worsen quality of life, and increase healthcare resource utilization and costs. This study assessed the costs of common AEs in mCRC patients (pts) in the US. METHODS Adult mCRC pts treated with chemotherapy (chemo) or targeted therapies were identified from the Truven MarketScan databases (2009 - 2014). Up to the first 3 mCRC treatment episodes were considered. mCRC treatment episodes were categorized as with or without (w/o) AEs based on the occurrence of AEs, listed in product labels, during the episode. Total healthcare costs (medical and pharmacy; 2014 USD) were measured by mCRC treatment episode and reported per-patient-per-month (PPPM). mCRC treatment episodes with AEs were matched by type of treatment (monotherapy/combination, chemo, anti-VEGF, and anti-EGFR) and line of therapy to those w/o AEs. Adjusted total cost differences were estimated by comparing costs during mCRC treatment episodes with vs w/o AEs using multivariate two-part models, adjusting for potential confounding factors; 95% confidence intervals (CIs) and p-values were estimated with bootstrap. RESULTS A total of 4,158 mCRC pts with ≥ 1 mCRC treatment episode were included (mean age= 59 years; 58% male; 2261 [54%] with a 2nd and 1115 [27%] with a 3rdepisode). The most prevalent metastatic sites were liver (60%) and lung (14%). On average, 2 mCRC treatment episodes were observed per patient with an average length of 166 days per episode. Most mCRC treatments included chemo (96%) and were combination regimens (81%). CONCLUSIONS The most costly AEs were hematologic, followed by respiratory, CNS, cardiovascular, and endocrine/metabolic AEs in mCRC pts. [Table: see text].

1427PANALYSIS OF TREATMENT PATTERNS OF PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS (GIST) IN EU5

ABSTRACT Aim: Real world data on treatment (tx) patterns in advanced GIST is sparse; our study provides an overview of the distribution of advanced GIST patients (pts) in lines of therapy and tx regimen. Methods: 161 tx records in EU5 (Germany, France, Spain, Italy, UK) were analyzed with a cross-sectional GIST enhanced tumor study (ETS) set up by IMS Health. The ETS entails information on pts demographics, full tx history and information on supportive therapies. Each medical record was analyzed with regards to current and historic therapies and regimen. Results: Distribution of pts (n=161) across lines of therapy and tx regimen is summarized in the table. While 77.5% of pts are in 1st therapy, 22.5% are in 2nd therapy. Patients that are in 3rd line therapy and beyond were not taken in consideration for this analysis. 86% of 1st therapy pts are receiving imatinib (IM)400 while 10% receive IM800, 2% receive sunitinib (SUN), 1% are on supportive* therapy and 1% are on other TKIs. 93% of pts in 2nd therapy had IM400 and 7% had SUN as their 1st therapy. Among the 2nd therapy pts who had IM400 as their 1st therapy, 72.5% receive SUN, 15% IM800; 10% IM400 and 2.5% regorafenib (REG). Among the 2nd therapy pts who had SUN as their 1st therapy, 33% receive SUN and 67% IM400. Distribution of patients# Tx Regimen 1st (77.5%) 2nd (22. 5%) IM400 in 1st therapy (93%) SUN in 1st therapy (7%) IM400 86% 10% 67% IM800 10% 15% - SUN 2% 72.5% 33% Supportive* 1% - - Other TKIs 1% - - REG - 2.5% - #Patients that are in 3rd line therapy and beyond were not taken in consideration for this analysis *Supportive: All molecules excl cytostatic drugs Source: IMS ETS Q4 2013, EU5 countries Conclusions: This analysis suggests that advanced GIST is treated with TKIs per guideline recommendations in EU5. However, non-evidence based practice was observed. Patients were continued with IM400 as 2nd therapy even though it is not recommended. The use of SUN in 1st therapy is likely to be due to IM intolerance; however, the rationale for treating these patients with IM400 as 2nd therapy is unclear. Disclosure: K. Jehle, M. Rabiller, S. Grippon and G. Haas: The study detailed in the abstract was funded by Bayer Healthcare Pharmaceuticals, Inc.; C. Ngai, A.F. Mohamed and J. Chang: is an employee of Bayer Healthcare Pharmaceuticals, Inc. The study detailed in the abstract was funded by Bayer Healthcare Pharmaceuticals, Inc.