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However, regulatory decisions vary globally, with some drugs withdrawn in the US remaining approved in Japan. We conducted a cross-sectional analysis of Japanese professional society guidelines, evaluating recommendations for seven accelerated approval cancer drugs withdrawn from the US market but retained in Japan. We assessed for level of evidence and level of treatment preference ratings with consensus across guidelines issued by the corresponding Japanese professional societies. Four of the seven drugs (57%) were recommended as highly or moderately preferred treatment options in Japanese guidelines: gemtuzumab ozogamicin for acute myeloid leukemia, gefitinib for EGFR-positive non-small cell lung cancer, bevacizumab for HER2-negative metastatic breast cancer, and atezolizumab with nab-paclitaxel for PD-L1-positive triple-negative breast cancer. Detailed analysis of regulatory history and background of guideline recommendation revealed discrepancies in the assessment of clinical benefits: gemtuzumab ozogamicin failed to demonstrate benefits amid safety concerns, while gefitinib, bevacizumab, and atezolizumab were more controversial, although they did not demonstrate improved overall survival in post-marketing trials. Despite regulatory withdrawal in the US due to unproven clinical benefits, drugs retained in Japan received positive guideline recommendations. This finding highlights regional variations in regulatory decisions and different approaches to benefit-risk assessments, suggesting a need for improved transparency in Japan\u2019s regulatory decisions and guideline recommendations, with clearer justifications for endorsing drugs that are considered to have unproven clinical benefits in the US.<\/jats:p>","DOI":"10.1007\/s10637-025-01524-9","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T06:10:12Z","timestamp":1743833412000},"page":"311-317","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["US FDA\u2013accelerated approvals and subsequent withdrawals: influence on Japanese clinical oncology practice guidelines"],"prefix":"10.1007","volume":"43","author":[{"given":"Hayase","family":"Hakariya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tanimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"1524_CR1","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1001\/jamainternmed.2019.0462","volume":"179","author":"B Gyawali","year":"2019","unstructured":"Gyawali B, Hey SP, Kesselheim AS (2019) Assessment of the clinical benefit of cancer drugs receiving accelerated approval. 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Thus, institutional review board approval and patients' informed consent were not necessary.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"T.T. receives personal fees from Medical Network Systems MNES Inc., outside the submitted work. A.O. receives personal fees from MNES Inc., Becton, Dickinson and Company, Taiho Pharmaceutical Co., Ltd., and Kyowa Kirin Inc., outside the submitted work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}