Chicago, IL (UroToday.com) Dr. Vaishampayan provided an excellent walk down memory lane, highlighting the landmark trials in kidney cancer over the last 20 years at this morning’s ASCO 2017 annual meeting session “Evolving Treatment Paradigm in Renal Cell Carcinoma.”
Dr. Vaishampayan started by highlighting SEER data that suggests that although the incidence of kidney cancer has increased over the past 40 years, the mortality rates have essentially stayed the same over this time period. IL-2 has been approved for treatment of advanced RCC since 1992 and results of 255 patients who received high-dose IL-2 therapy demonstrated an objective response rate (ORR) of 14%, complete response (CR) rate of 5%, partial response (PR) rate of 9% [1]. Data from the PROCLAIMSM trial of 352 patients receiving targeted therapy prior to or following high dose IL-2 demonstrated 4% CR, 13% PR, 39% stable disease (SD), and 43% progressive disease (PD) with IL-2, demonstrating a clinical benefit for patients who progressed on targeted therapy [2]. Conclusions from these IL-2 studies include the fact that certain patients treated with IL-2 will have a CR+PR (~15%), however the majority of these patients are intermediate and not high risk. Furthermore, despite the toxicities of IL-2, they are predictable and manageable, and it is a remarkably time and cost effective therapy. Dr. Vaishampayan then highlighted that based on a meta-analysis of phase III trials of cytoreductive nephrectomy in the interferon era, patients derive a statistically significant survival benefit [3]. However, as Dr. Vaishampayan notes, based on recent SEER data, only 1/3 of patients receive cytoreductive nephrectomy.
The early to mid-2000’s saw the development of TKI therapy. In 2007, Escudier et al. demonstrated that sorafenib compared to placebo prolonged progression-free survival (PFS) in patients with advanced RCC [4]. Additional trials that year also demonstrated improved PFS for sunitinib compared to interferon-alfa [5], as well as temsirolimus compared to interferon alfa, particularly in patients with poor prognosis [6]. In 2013, we saw the COMPARZ trial of pazopanib vs sunitinib in the 1st line for mRCC, demonstrating comparable efficacy between the two agents (median OS: sunitinib 29.3 months vs pazopanib 28.4 months), although with improved tolerability with pazopanib [7].
There is currently a plethora of phase III trials for second line therapy for patients with mRCC that have reported in the past few years. In 2015, the METEOR trial (cabozantinib vs everolimus) reported that PFS was longer in the cabozantinib arm compared to everolimus (HR for death 0.67, 95%CI 0.51-0.89) [8]. A recent updated analysis of this data demonstrated improved OS, delayed disease progression, and improved ORR for cabozantinib [9]. Finally, Motzer and colleagues assessed lenvatinib + everolimus and lenvatinib alone and found that PFS for patients treated with combination therapy (HR 0.40, 95%CI 0.24-0.68) and lenvatinib alone (HR 0.61, 95%CI 0.38-0.98) was improved compared to everolimus alone [10].
In conclusion, there are many novel immune therapy trials on-going, but the landmark trials have established efficacy of multiple therapies in advanced RCC. As Dr. Vaishampayan notes, with multiple therapies available, a discussion of risk/reward ratio should occur with each patient. Certainly, we have hopes that single biomarker driven therapy may eventually be possible, however this is not currently available to ultimately guide precise treatment management.
Presented By: Ulka N. Vaishampayan, Karmanos Cancer Institute, Detroit, MI, USA
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md
References:
1. Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995 Mar;13(3):688-696.
2. Clark JI, Wong MK, Kaufman HL, et al. Impact of sequencing targeted therapies with high-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients with Metastatic Renal Cell Carcinoma from an Ongoing Observational IL-2 Clinical Trial: PROCLAIMSM. Clin Genitourin Cancer 2017 Feb;15(1):31-41.
3. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 2004 Mar;171(3):1071-1076.
4. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):125-134.
5. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007 Jan 11;356(2):115-124.
6. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med2007 May 31;356(22):2271-2281.
7. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013 Aug 22;369(8):722-731.
8. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015 Nov 5;373(19):1814-1825.
9. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in advanced renal cell carcinoma (METEOR): final results form a randomized, open-label, phase 3 trial. Lancet Oncol 2016 Jul;17(7):917-927.
10. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomized, phase 2, open-label, multicenter trial. Lancet Oncol 2015 Nov;16(15):1473-1482.
at the 2017 ASCO Annual Meeting – June 2 – 6, 2017 – Chicago, Illinois, USA
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