Original Article: Clinical Investigation Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan Kenichi Harada, 1 Masahiro Nozawa, 2 Motohide Uemura, 3 Katsunori Tatsugami, 4 Takahiro Osawa, 5 Kazutoshi Yamana, 6 Go Kimura, 7 Masato Fujisawa, 1 Norio Nonomura, 3 Masatoshi Eto, 4 Nobuo Shinohara, 5 Yoshihiko Tomita, 6 Yukihiro Kondo, 7 Kenya Ochi, 8 Yoshio Anazawa 9 and Hirotsugu Uemura 2 1 Division of Urology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe, 2 Department of Urology, Kindai University Faculty of Medicine, 3 Department of Urology, Osaka University Graduate School of Medicine, Osaka, 4 Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 5 Department of Urology, Hokkaido University, Sapporo, 6 Department of Urology, Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 7 Department of Urology, Nippon Medical School, Tokyo, 8 Ono Pharmaceutical, Osaka, and 9 Bristol-Myers Squibb, Tokyo, Japan Abbreviations & Acronyms AE = adverse event BMI = body mass index ECOG = Eastern Cooperative Oncology Group eGFR = estimated glomerular filtration rate HR = hazard ratio IFN-a = interferon alpha IL-2 = interleukin-2 mRCC = unresectable or metastatic renal cell carcinoma MSKCC = Memorial Sloan Kettering Cancer Center mTOR = mammalian target of rapamycin mTORi = mammalian target of rapamycin inhibitor ORR = overall response rate OS = overall survival PFS = progression-free survival PS = performance status RCC = renal cell carcinoma TKI = tyrosine kinase inhibitor VEGF = vascular endothelial growth factor VEGFR = vascular endothelial growth factor receptor Correspondence: Hirotsugu Uemura M.D., Department of Urology, Kindai University Faculty of Medicine, 377-2 Ono- Higashi, Osakasayama City, Osaka 589-8511, Japan. Email: huemura@med.kindai.ac.jp Received 12 April 2018; accepted 13 September 2018. Online publication 21 October 2018 Objectives: To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. Methods: A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. Results: Of 277 eligible patients, 266, 170 and 77 received first-, second- and third-line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first- line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second-line treatment, tyrosine kinase inhibitor–tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor–mammalian target of rapamycin inhibitor (14.1%) and cytokine–tyrosine kinase inhibitor (14.1%). With a median follow-up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first-line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first-line tyrosine kinase inhibitors for ≥6 months. Conclusions: The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real-world setting in Japan. Tyrosine kinase inhibitor–tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first-line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options. Key words: carcinoma, cohort studies, Japan, medical records, molecular targeted therapy, renal cell. Introduction Advanced or mRCC has historically had a poor prognosis, with a median survival rate of approximately 13 months between 1996 and 2003. 1 However, 5-year survival has increased over time from 7.3% (1992–1995) to 12.3% (2003–2009). 2 In Japan, the National Cancer Institute estimated that 23 082 Japanese people were diagnosed with renal/urothelial cancer in 2011 (excluding bladder cancer), with 8793 deaths resulting from this disease in 2014. 3,4 Over the past decade, new therapies targeting VEGF, tyrosine kinase and mTOR pathways have improved PFS and OS. 5 However, an OS benefit over the previous standard of care, 202 © 2018 The Japanese Urological Association International Journal of Urology (2019) 26, 202--210 doi: 10.1111/iju.13830