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Meta-Analysis
. 2024 Jun 1;279(6):1025-1035.
doi: 10.1097/SLA.0000000000006084. Epub 2023 Aug 28.

Surrogacy of Recurrence-free Survival for Overall Survival as an Endpoint of Clinical Trials of Perioperative Adjuvant Therapy in Hepatobiliary-pancreatic Cancers: A Retrospective Study and Meta-analysis

Taisuke Imamura  1 , Katsuhisa Ohgi  1 , Keita Mori  2 , Ryo Ashida  1 , Mihoko Yamada  1 , Shimpei Otsuka  1 , Katsuhiko Uesaka  1 , Teiichi Sugiura  1
Affiliations
Meta-Analysis

Surrogacy of Recurrence-free Survival for Overall Survival as an Endpoint of Clinical Trials of Perioperative Adjuvant Therapy in Hepatobiliary-pancreatic Cancers: A Retrospective Study and Meta-analysis

Taisuke Imamura et al. Ann Surg. .

Abstract

Objective: To assess the correlation between recurrence-free survival (RFS) and overall survival (OS) in the hepatobiliary-pancreatic (HBP) surgical setting to validate RFS as a surrogate endpoint.

Background: Reliable surrogate endpoints for OS are still limited in the field of HBP surgery.

Methods: We analyzed patients who underwent curative resection for HBP disease [986 patients with pancreatic ductal adenocarcinoma (PDAC), 1168 with biliary tract cancer (BTC), 1043 with hepatocellular carcinoma, and 1071 with colorectal liver metastasis] from September 2002 to June 2022. We also conducted meta-analyses of randomized controlled trials of neoadjuvant or adjuvant therapy to validate the surrogacy in PDAC and BTC.

Results: Correlation coefficients between RFS and OS were low for hepatocellular carcinoma ( p = 0.67) and colorectal liver metastasis ( p = 0.53) but strong for PDAC ( p = 0.80) and BTC ( p = 0.75). In a landmark analysis, the concordance rates between survival or death at 5 years postoperatively and the presence or absence of recurrence at each time point (1, 2, 3, and 4 years) were 50%, 70%, 74%, and 77% for PDAC and 54%, 67%, 73%, and 78% for BTC, respectively, both increasing and reaching a plateau at 3 years. In a meta-analysis, the correlation coefficients for the RFS hazard ratio and OS hazard ratio in PDAC and BTC were p = 0.88 ( P < 0.001) and p = 0.87 ( P < 0.001), respectively.

Conclusions: Three-year RFS can be a reliable surrogate endpoint for OS in clinical trials of neoadjuvant or adjuvant therapy for PDAC and BTC.

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Conflict of interest statement

K.M. has received honoraria from Chugai Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, and Eli Lilly Japan K.K. The remaining authors report no conflicts of interest.

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