Presentation (CTI)

OBJECTIVES: Accelerated approval pathways enable earlier access to oncology drugs despite substantial uncertainty regarding clinical benefit. This challenge becomes particularly important when indications withdrawn in the U.S. remain authorized in other countries. This study aims to evaluate whether FDA-withdrawn accelerated-approval oncology indications remained approved in China, Japan, and South Korea; to examine the regulatory and evidentiary factors associated with divergent cross-national decisions; and to estimate the frequency with which post-marketing confirmatory trials or real-world evidence are required before reimbursement.
METHODS: We identified oncology indications withdrawn after FDA accelerated approval between 1992 and 2025. Age-standardized incidence, prevalence, and mortality rates obtained from the Global Burden of Disease study were used to characterize disease burden. Data on efficacy and safety, post-marketing requirements, and insurance coverage were collected from publicly available databases across the four countries.
RESULTS: As of December 2025, 32 oncology indications had been withdrawn in the U.S. Of these, 7 remained approved in China, 7 in Japan, and 14 in South Korea with disease burden varying across four countries. Among indications remaining approved outside the U.S., 88% relied on no additional clinical evidence beyond that supporting the original FDA accelerated approval, leaving efficacy uncertainty unresolved. Meanwhile, 3 and 7 indications were withdrawn in China and South Korea, respectively. Requirements for confirmatory trials differed across countries, particularly between the U.S. and South Korea (China: P = 0.25; Japan: P = 0.06; South Korea: P < 0.01). Only a minority of indications subsequently received reimbursement recommendations after regulatory authorization.
CONCLUSIONS: Accelerated approval drugs are often authorized in China, Japan, and South Korea despite unresolved efficacy uncertainty and limited new supporting evidence. In settings lacking mandatory confirmatory trials, uncertainty may extend into routine clinical use and reimbursement decisions, highlighting the need for stronger post-marketing evidence generation and reassessment mechanisms.