Meta-analysis for the Association between Overall Survival and Progression-Free Survival in Gastrointestinal Stromal Tumor

Abstract

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 followup 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 ¼ 0.52; second line ¼ 0.80; third-and laterline ¼ 0.70) and imatinib showed a stronger association (0.91) than other evaluated treatments (À0.26 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.

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

“…In gastric cancer, Liu et al reported that PFS is strongly corrected with OS based on a NICE correlation model [26]. Özer-Stillman et al identified a strong relationship between median OS and PFS among gastrointestinal stromal tumor patients, especially in later lines of therapy based on meta-analysis [27]. However, others reached a different conclusion, questioning the validity of PFS as a surrogate endpoint for OS in gastric cancer patients [28, 29].…”

TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials

“…Progression-free survival (PFS) and disease-free survival is suggested as an appropriate surrogate endpoint in phase II or III clinical trial conducted in solid tumour patients. The correlation between surrogate endpoints and OS has been validated in many types of cancer, including breast cancer, colorectal cancer, and lung cancer (Buyse et al , 2000b, 2007, 2009; Sargent et al , 2005; Petrelli and Barni, 2014; Blumenthal et al , 2015; Ozer-Stillman et al , 2015). However, there is no study that has evaluated the correlation between surrogate endpoints and OS in advanced HCC.…”

Relationship between response rates and median progression‐free survival in non‐Hodgkin's lymphoma: A meta‐analysis of published clinical trials

“…However, in recent past (since 1990), a trend of decreased use of OS and increased use of event‐free survival/PFS as a primary endpoint has occurred in NHL . Furthermore, the surrogacy of PFS for OS has been established in various cancer settings such as colorectal cancer, gastrointestinal stromal tumors, metastatic prostate cancer, and hematological malignancies, including chronic lymphocytic leukemia, NHL, and MM . For instance, Lee et al found a good correlation ( R 2 = 0.90) between PFS and OS in aggressive NHL, although they could not establish the same correlation between PFS and OS in indolent NHL.…”