Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma: Pooled analysis of individual patient data from randomized controlled trials.

Authors

null

Ulrich Ronellenfitsch

University Hospital Halle (Saale), Department of Visceral, Vascular and Endocrine Surgery, Halle (Saale), Germany

Ulrich Ronellenfitsch , Katrin Jensen , Svenja Seide , Meinhard Kieser , Matthias Schwarzbach , Tracy E Slanger , Bryan Burmeister , David Paul Kelsen , Donna Niedzwiecki , Guillaume Piessen , Christoph Schumacher , Susan Urba , Cornelis J. H. Van De Velde , Marc Ychou , Ralf Dieter Hofheinz , Sylvie Lorenzen

Organizations

University Hospital Halle (Saale), Department of Visceral, Vascular and Endocrine Surgery, Halle (Saale), Germany, University Heidelberg, Institute of Medical Biometry and Informatics, Heidelberg, Germany, University of Heidelberg, Institute of Medical Biometry and Informatics, Heidelberg, Germany, Klinikum Frankfurt-Höchst, Department of General, Visceral, Vascular and Thoracic Surgery, Frankfurt, Germany, Senior Consultant, Palo Alto, CA, University of Queensland, Hervey Bay Hospital, Fraser Coast, Australia, Memorial Sloan Kettering Cancer Center, New York, NY, Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, Department of Digestive and Oncologic Surgery, Claude Huriez University Hospital, Lille, France, Department of Surgery, Klinikum Rechts der Isar, Technische Univerisität, München, Germany, University of Michigan Cancer Center, Ann Arbor, MI, Leiden University Medical Center, Department of Surgery, Leiden, Netherlands, ICM Val d'Aurelle, University of Montpellier, Montpellier, France, University Medical Center Mannheim, Tagestherapiezentrum am ITM, Mannheim, Germany, Third Department of Internal Medicine (Hematology/Medical Oncology), Klinikum Rechts der Isar, Technische Universitat Munchen, Munich, Germany

Research Funding

No funding received
None

Background: Disease-free survival (DFS) is an appealing surrogate endpoint for overall survival (OS) in trials on neoadjuvant or adjuvant cancer therapy, because it is available faster and with less follow-up effort. The aim of this study was to assess if DFS can be a valid surrogate endpoint for OS when comparing neoadjuvant treatment followed by surgery to surgery alone for gastroesophageal adenocarcinoma. Methods: Individual patient data (IPD) from eight randomized controlled trials (n = 1,126 patients) which compared neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma were used for the analysis. Correlation between OS-time and DFS-time was calculated. Kaplan-Meier survival curves and corresponding hazard ratios (HRs) for treatment effects were separately determined for each trial. Subsequently, HRs were pooled in a meta-analysis using a random-effects model. An error-in-variables linear regression model was used to compare observed and predicted values. The minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS was estimated by calculating the surrogate threshold effect. Results: OS-time correlated strongly with DFS-time. HRs for OS and DFS were highly similar for all single trials. The meta-analysis yielded almost identical overall HRs for treatment effects on OS and DFS. The determination coefficient for the association between HRs for OS and DFS was 0.912 (95% confidence interval 0.75-1.0), indicating a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect was calculated at 0.79, indicating that a future trial yielding a hazard ratio for the treatment effect on DFS < 0.79 could be expected with a 95% probability to yield a hazard ratio for the treatment effect on OS < 1. Conclusions: DFS and OS strongly correlate both after neoadjuvant therapy followed by surgery and after surgery alone for gastroesophageal adenocarcinoma. Likewise, the treatment effects on the two endpoints are very similar. Consequently, DFS can be regarded an appropriate surrogate endpoint for OS in trials on neoadjuvant therapy for gastroesophageal adenocarcinoma.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Esophageal or Gastric Cancer

Citation

J Clin Oncol 38: 2020 (suppl; abstr 4533)

DOI

10.1200/JCO.2020.38.15_suppl.4533

Abstract #

4533

Poster Bd #

141

Abstract Disclosures