Abstract 1943: Disparities in multinational phase III liver cancer clinical trials by regions of the world
Authors: Maldonado J. Alberto , McGlynn Katherine A. , Greten Tim F. , Monge Cecilia 
Published: April 2023

Abstract
Background: The incidence and etiology of liver cancer varies widely across geographical regions. Etiological factors involved in hepatocarcinogenesis, which vary according to geographical location seem to play an important role in therapeutic efficacy. According to the International Agency for Research on Cancer 2020 report, the combined percentage of total hepatocellular carcinoma (HCC) and biliary tract carcinoma (BTC) cases in the world was 72.3% from Asia, 9.9% from the Americas, 9.8% from Europe, 7.4% from Africa, and 0.5% from Oceania. We describe the regional accrual of multinational phase III liver cancer clinical trials in the last ten years.
Methods: We performed a database search in PubMed, Embase, and Web of Science: Core Collection for multinational phase III clinical trials of HCC or BTC, studying first and second line treatments published in the last 10 years (08/2012 - 08/2022). Trials meeting these criteria were identified and the percentage of regional distribution was calculated.
Results: 17 multinational phase III clinical trials studying treatments for HCC and BTC were identified; 16 reported regional patient characteristics. The trials enrolled a total of 10,834 patients, of which 48.6% were from Asia, 17.1% from Europe, 8.5% from the Americas, 0.7% from Oceania, and 0.1% from Africa. The remaining patients were missing regional data.
Conclusions: In phase III multinational liver cancer studies seeking FDA approval does not include patients from all geographical regions.
Table 1: Regional characteristics of multinational phase III clinical trials of Liver Cancer Trial name, identifier Treatment Total patients Europe Africa South America North America Asia Oceania Other/Multiple BRISK-FLNCT00858871 Brivanib, Sorafenib 1155 269 7 152* 718 9 - BRISK-PSNCT00825955 Brivanib 395 166 - 67* 162 - - NCT00699374 Sunitinib, Sorafenib 1074 - - - - 812 - 262 SEARCHNCT0901901 Sorafenib, Erlotinib 720 369 - 173* 178 - - REACHNCT01140347 Ramucirumab 565 248 - 65* 252 - - NCT01009593 Linifanib, Sorafenib 1035 - - - - 689 - 346 RESORCENCT01774344 Regorafenib 573 - - - - 216 - 357 NCT01761266 Lenvatinib, Sorafenib 954 - - - - 640 - 314 CELESTIALNCT01908426 Cabozantinib 707 339 - - 167 175 26 - REACH-2NCT02435433 Ramucirumab 292 - - - - 141 - 151 ClarIDHyNCT02989857 Ivosidenib 185 49 - - 124 12 - - IMbrave150NCT03434379 Atezolizumab, Bevacizumab, Sorafenib 501 - - - - - - 501 KEYNOTE-240NCT02702401 Pembrolizumab 413 139 - - 37 157 - 80 TOPAZ-1NCT03875235 Durvalumab, Gemcitabine, Cisplatin - - - - 374 - 311 - CheckMate459NCT02576509 Nivolumab, Sorafenib - - - - 295 - 448 - COSMIC-312NCT03755791 Cabozantinib, Atezolizumab, Sorafenib 276 - 77 57 241 44 142 - *Includes both North and South America
Citation Format: J. Alberto Maldonado, Katherine A. McGlynn, Tim F. Greten, Cecilia Monge. Disparities in multinational phase III liver cancer clinical trials by regions of the world [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1943.