Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial

作者：Janet E. Brown, Kara‐Louise Royle, Walter M. Gregory, Christy Ralph, Anthony Maraveyas, Omar Din, Timothy Eisen, Paul Nathan, Tom Powles, Richard Griffiths, Robert J. Jones, Naveen Vasudev, Matthew Wheater, Abdel Hamid, Tom Waddell, R. McMenemin, Poulam M. Patel, James Larkin, Guy Faust, Adam Martin, Jayne Swain, Janine Bestall, Christopher McCabe, David Meads, Vicky Goh, Tze Min Wah, Julia Brown, Jenny Hewison, Peter J. Selby, Fiona Collinson, Judith Carser, Gopalakrishnan Srinivasan, Fiona Thistlewaite, Ashraf Azzabi, Mark Beresford, David Farrugia, M. Decatris, Carys Thomas, Joanna Gale, James J McAleer, Alison Clayton, Ekaterini Boleti, T. Geldart, Santhanam Sundar, J.F. Lester, Nachi Palaniappan, Mohan Hingorani, Khaliq Rehman, Mohammad Adil Khan, Naveed Sarwar, Janine Graham, Alastair Thomson, Narayanan Srihari, Denise Sheehan, R. Srinivasan, Omar Khan, Andrew Stockdale Jane Worlding, Stergios Boussios, N Stuart, Carey MacDonald-Smith, Falalu Danwata, Duncan McLaren, Aravindhan Sundaramurthy, Anna Lydon, S. Beesley, Kathryn Lees, Mohini Varughese, Emma Gray, Angela Scott, Mark Baxter, Anna Mullard, Pasquale F. Innominato, Gaurav Kapur, Anil Kumar, Natalie Charnley, Caroline Manetta, Prabir Chakraborti, Prantik Das, Sarah Rudman, Henry F. Taylor, Christos Mikropoulos, Martin Highley, D. Muthukumar, Anjali Zarkar, Roy Vergis, Seshadri Sriprasad, Patryk Brulinski, Amanda Clarke, Richard Osbourne, Melanie Harvey, Renata Dega, Geoffrey Sparrow, U. Barthakur, Erica Beaumont, Caroline Manetta, Agnieszka Michael, Emilio Porfiri, Faisal Azam, Ravi Kodavtiganti · 发表于：The Lancet Oncology · 年份：2023 · DOI：10.1016/s1470-2045(22)00793-8 · 被引用次数：84 · 研究领域：Renal cell carcinoma treatment、Multiple and Secondary Primary Cancers、Bladder and Urothelial Cancer Treatments

BACKGROUND: Temporary drug treatment cessation might alleviate toxicity without substantially compromising efficacy in patients with cancer. We aimed to determine if a tyrosine kinase inhibitor drug-free interval strategy was non-inferior to a conventional continuation strategy for first-line treatment of advanced clear cell renal cell carcinoma. METHODS: This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done at 60 hospital sites in the UK. Eligible patients (aged ≥18 years) had histologically confirmed clear cell renal cell carcinoma, inoperable loco-regional or metastatic disease, no previous systemic therapy for advanced disease, uni-dimensionally assessed Response Evaluation Criteria in Solid Tumours-defined measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) at baseline to a conventional continuation strategy or drug-free interval strategy using a central computer-generated minimisation programme incorporating a random element. Stratification factors were Memorial Sloan Kettering Cancer Center prognostic group risk factor, sex, trial site, age, disease status, tyrosine kinase inhibitor, and previous nephrectomy. All patients received standard dosing schedules of oral sunitinib (50 mg per day) or oral pazopanib (800 mg per day) for 24 weeks before moving into their randomly allocated group. Patients allocated to the drug-free interval strategy group then had a treatment ...