Real-life patterns of use, safety and effectiveness of sunitinib in first-line therapy of metastatic renal cell carcinoma: the SANTORIN cohort study
Corresponding Author
Pernelle Noize
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
Correspondence to: P. Noize, Service de Pharmacologie Médicale, CHU et Université de Bordeaux, Zone Nord Carreire, Bâtiment 1A, Case 36, 146 rue Léo Saignat 33076 Bordeaux Cedex, France. E-mail: [email protected]Search for more papers by this authorAngela Grelaud
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorJacques-Olivier Bay
CHU Clermont-Ferrand, Site Estaing et Centre Jean Perrin, Clermont-Ferrand, France
Search for more papers by this authorJean-Marie Ferrière
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorFlore Moulin
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorPhilip Robinson
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorAurelie Balestra
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorStéphanie Lamarque
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorMarie-Agnès Bernard
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorRégis Lassalle
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorMagali Rouyer
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorCécile Droz-Perroteau
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorNicholas Moore
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorAnnie Fourrier-Réglat
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorAlain Ravaud
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorCorresponding Author
Pernelle Noize
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
Correspondence to: P. Noize, Service de Pharmacologie Médicale, CHU et Université de Bordeaux, Zone Nord Carreire, Bâtiment 1A, Case 36, 146 rue Léo Saignat 33076 Bordeaux Cedex, France. E-mail: [email protected]Search for more papers by this authorAngela Grelaud
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorJacques-Olivier Bay
CHU Clermont-Ferrand, Site Estaing et Centre Jean Perrin, Clermont-Ferrand, France
Search for more papers by this authorJean-Marie Ferrière
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorFlore Moulin
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorPhilip Robinson
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorAurelie Balestra
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorStéphanie Lamarque
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorMarie-Agnès Bernard
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorRégis Lassalle
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorMagali Rouyer
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorCécile Droz-Perroteau
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
Search for more papers by this authorNicholas Moore
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorAnnie Fourrier-Réglat
Bordeaux PharmacoEpi, Inserm CIC1401, Bordeaux, France
CHU Bordeaux, Bordeaux, France
Bordeaux Population Health Research Centre, Pharmacoepidemiology team, Inserm U1219, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorAlain Ravaud
CHU Bordeaux, Bordeaux, France
University Bordeaux, Bordeaux, France
Search for more papers by this authorAbstract
Purpose
To investigate sunitinib in the real-life first-line treatment of metastatic renal cell carcinoma (mRCC).
Methods
SANTORIN is a French observational multicentre cohort. Patients initiating sunitinib in first-line mRCC therapy were included (January 2008 to April 2010) and followed for 24 months. Data were collected from medical files. The outcomes were 24-month overall survival (OS) and progression-free survival (PFS), response and safety.
Results
Three hundred two patients were included: median age, 64.8 years; male, 73.2%; clear cell mRCC, 83.1%; prior nephrectomy, 85.4%; >1 metastatic sites, 64.2%; brain metastases, 6.3%; ECOG-PS ≥ 2, 9.9%. Median duration of first-line therapy with sunitinib was 10.7 months. Initial sunitinib dose was 50 mg/day for 83.4% of patients; dose reduction occurred in 65.2%. Sunitinib was discontinued in 73.2% of the patients: for progression (61.1%), death (31.2%) or adverse events (6.8%). More than half (58.3%) had grade ≥3 adverse events, mainly hypertension (12.6%) and hand–foot syndrome (12.3%). The 24-month OS and PFS rates [95%CI] were 49.5% [43.7;55.0] and 16.4% [12.5;20.9], respectively. Median OS was 23.6 months [20.2;–] and median PFS 8.4 months [7.6;9.9]. Overall best response rate was 31.1%.
Conclusions
Results from this large observational study suggest that effectiveness of sunitinib in first-line mRCC as predicted by clinical trials is maintained in real-life clinical practice. The expected benefit in poor-prognosis patients that were not evaluated in the pivotal clinical trial remains; however, questionable and long-term safety monitoring is still warranted. Copyright © 2017 John Wiley & Sons, Ltd.
References
- 1Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer. Available at: http://globocan.iarc.fr [23 Oct 2015].
- 2Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996; 335: 865–875. https://doi.org/10.1056/NEJM199609193351207.
- 3Ljungberg B. The role of metastasectomy in renal cell carcinoma in the era of targeted therapy. Curr Urol Rep 2013; 14: 19–25. https://doi.org/10.1007/s11934-012-0293-6.
- 4Motzer RJ, Bacik J, Schwartz LH, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 2004; 22: 454–463. https://doi.org/10.1200/JCO.2004.06.132.
- 5Figlin R, Sternberg C, Wood CG. Novel agents and approaches for advanced renal cell carcinoma. J Urol 2012; 188: 707–715. https://doi.org/10.1016/j.juro.2012.04.108.
- 6Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–134. https://doi.org/10.1056/NEJMoa060655.
- 7Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103–2111. https://doi.org/10.1016/S0140-6736(07)61904-7.
- 8Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356: 2271–2281. https://doi.org/10.1056/NEJMoa066838.
- 9Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115–124. https://doi.org/10.1056/NEJMoa065044.
- 10Sternberg CN, Hawkins RE, Wagstaff J, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer 2013; 49: 1287–1296. https://doi.org/10.1016/j.ejca.2012.12.010.
- 11Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 3584–3590. https://doi.org/10.1200/JCO.2008.20.1293.
- 12 European Medicines Agency. Sutent : EPAR - Product Information (last updated 14/04/2016) [Internet]. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000687/WC500057737.pdf [13 Nov 2016].
- 13Negrier S, Gravis G, Perol D, et al. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. Lancet Oncol 2011; 12: 673–680. https://doi.org/10.1016/S1470-2045(11)70124-3.
- 14Motzer RJ, Hutson TE, Olsen MR, et al. Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma. J Clin Oncol 2012; 30: 1371–1377. https://doi.org/10.1200/JCO.2011.36.4133.
- 15Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013; 369: 722–731. https://doi.org/10.1056/NEJMoa1303989.
- 16Yoo C, Kim JE, Lee JL, et al. The efficacy and safety of sunitinib in korean patients with advanced renal cell carcinoma: high incidence of toxicity leads to frequent dose reduction. Jpn J Clin Oncol 2010; 40: 980–985. https://doi.org/10.1093/jjco/hyq073.
- 17Ansari J, Fatima A, Fernando K, et al. Sunitinib in patients with metastatic renal cell carcinoma: Birmingham experience. Oncol Rep 2010; 24: 507–510.
- 18Yuasa T, Tsuchiya N, Urakami S, et al. Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib. BJU Int 2012; 109: 1349–1354. https://doi.org/10.1111/j.1464-410X.2011.10534.x.
- 19Feinberg BA, Jolly P, Wang ST, et al. Safety and treatment patterns of angiogenesis inhibitors in patients with metastatic renal cell carcinoma: evidence from US community oncology clinics. Med Oncol 2012; 29: 786–794. https://doi.org/10.1007/s12032-011-9922-z.
- 20Castellano D, Duh MS, Korves C, et al. Safety and treatment patterns of angiogenesis inhibitors in patients with advanced renal cell carcinoma in Spain. Expert Opin Drug Saf 2013; 12: 455–463. https://doi.org/10.1517/14740338.2013.781581.
- 21Hess G, Borker R, Fonseca E. Treatment patterns: targeted therapies indicated for first-line management of metastatic renal cell carcinoma in a real-world setting. Clin Genitourin Cancer 2013; 11: 161–167. https://doi.org/10.1016/j.clgc.2012.10.003.
- 22Matsubara N, Mukai H, Naito Y, et al. First experience of active surveillance before systemic target therapy in patients with metastatic renal cell carcinoma. Urology 2013; 82: 118–123. https://doi.org/10.1016/j.urology.2013.03.035.
- 23Oh WK, McDermott D, Porta C, et al. Angiogenesis inhibitor therapies for advanced renal cell carcinoma: toxicity and treatment patterns in clinical practice from a global medical chart review. Int J Oncol 2014; 44: 5–16. https://doi.org/10.3892/ijo.2013.2181.
- 24Atkinson BJ, Kalra S, Wang X, et al. Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules. J Urol 2014; 191: 611–618. https://doi.org/10.1016/j.juro.2013.08.090.
- 25Wagstaff J, Jones R, Hawkins R, et al. Treatment patterns and clinical outcomes in patients with renal cell carcinoma in the UK: insights from the RECCORD registry. Ann Oncol 2016; 27: 159–165. https://doi.org/10.1093/annonc/mdv504.
- 26Heng DY, Choueiri TK, Rini BI, et al. Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann Oncol 2014; 25: 149–154. https://doi.org/10.1093/annonc/mdt492.
- 27Fourrier-Réglat A, Smith D, Rouyer M, et al. Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort. Target Oncol 2014; 9: 311–319. https://doi.org/10.1007/s11523-013-0296-3.
- 28Fourrier-Réglat A, Noize P, Facon T, et al. Real-life patterns of use and effectiveness of bortezomib: the VESUVE cohort study. Leuk Lymphoma 2014; 55: 848–854. https://doi.org/10.3109/10428194.2013.806801.
- 29Fourrier-Reglat A, Droz-Perroteau C, Benichou J, et al. Impact of prescriber nonresponse on patient representativeness. Epidemiology 2008; 19: 186–190. https://doi.org/10.1097/EDE.0b013e31816326e9.
- 30Mejean A, Lebret T. Prise en charge of metastatic renal carcinoma. Prog Urol 2008; 18(Suppl 7): S298–S308. https://doi.org/10.1016/S1166-7087(08)74558-5.
- 31Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002; 20: 289–296.
- 32Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 3.2015. J Natl Compr Canc Netw 2015; 13: 151–159.
- 33Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol 2015; 67: 913–924. https://doi.org/10.1016/j.eururo.2015.01.005.
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