A systematic review examining the relationship between progression-free survival and overall survival in adults with untreated metastatic pancreatic cancer.

Abstract

e15724 Background: The majority of pancreatic cancers are diagnosed in advanced stages with a median survival of 3 to 5 months. From 2005 to 2012, the US Food and Drug Administration approved 41 oncology drugs; surrogate endpoints were used in 84% of the trials providing the basis of approval. The aim of this systematic review was to evaluate the relationship between PFS/TTP and OS in metastatic pancreatic cancer. Methods: A systematic literature review used the Centre for Reviews and Dissemination principles to identify studies that reported median PFS or TTP and OS. We searched Medline, Medline In-Process, and Embase, with the following additional limits: English language and published 1/1990 to 7/ 2016. Selection criteria, defined a priori, included chemo, immuno or targeted therapy, randomized controlled studies (Phase 2 or 3) in patients with metastatic pancreatic cancer. Studies were assessed for quality using the Cochrane Risk of Bias tool and the Jadad scale. Studies were excluded if full-text articles were not available, and if patients received chemotherapy plus radiotherapy or surgery. Correlation analyses and weighted linear regression were used to assess the association between median PFS/TTP and median OS. The distributions of median PFS/TTP and OS were examined using scatterplots. Results: 1,691 studies were identified. After screening by title and abstract, 212 full articles were assessed, of which 28 studies (evaluating 6,734 patients) met the selection criteria. The mean median PFS/TTP and OS were, respectively, 3.82 months (range 1.2 to 6.8 months), and 7.06 months (range 2.5 to 11.9 months). The correlation coefficient was 0.837; 95% CI (0.734-0.903) indicating a very strong positive correlation between median OS and median PFS/TTP. Regression analysis indicated that median PFS/TTP was a highly significant predictor of median OS = 2.177 + 1.247 * median PFS/TTP (p < 0.001). Conclusions: The analysis demonstrates a very strong positive correlation of median PFS/TTP with median OS for the treatment of metastatic pancreatic cancer, which reinforces the hypothesis that PFS or TTP is a useful surrogate endpoint for OS in this cancer setting.