(UroToday.com) The 2024 ESMO annual meeting included a session on kidney cancer, featuring a presentation by Dr. Deepak Kilari discussing outcomes from the ORACLE study assessing novel combinations in non-clear cell RCC. Non clear cell RCC encompasses a heterogeneous group of histologies and comprised ~25% of all RCC diagnoses. Advances in the treatment of clear cell RCC have not translated directly to benefit non clear cell RCC. There is a paucity of data to guide the management of non-clear cell RCC due to the heterogeneity and rarity of these tumors. Limited data exists regarding the clinical activity of combination therapies in subtypes of advanced non-clear cell RCC. Moreover, the clinical activity of new combination therapies (including monotherapy IO), anti-VEGF, and mTOR inhibitors) in metastatic non clear cell RCC is not completely understood.
In this multicenter retrospective analysis, Dr. Kilari and colleagues evaluated the efficacy of combination systemic therapy from 2012-2024 in patients with non-clear cell RCC. Eligible patients included those with non-clear cell RCC and receipt of any combination regimens including IO-IO, IO-VEGF, mTOR-VEGF during any line of treatment. The primary endpoint was objective response rate assessed by investigator review. Secondary endpoints were progression- free survival, disease control rate, and overall survival.
There were 253 patients that received combination regimens. The median age was 59 years, 72% were male, and 64% were white. Histologies included papillary (38%), unclassified (34%), chromophobe (16%), translocation (8%), and other (4%). Overall, 23% had sarcomatoid and/or rhabdoid differentiation, 73% had prior nephrectomy, and 82% were IMDC intermediate/poor risk. There were 23% and 28% of patients that had liver and bone metastasis, respectively. The majority (69%) received combination treatment as first line:
Response by subgroup is as follows:
Objective response rate, disease control rate, and progression- free survival were significantly lower when combination regimens were utilized in second or later line compared to front line setting.
Dr. Kilari concluded his presentation by discussing outcomes from the ORACLE study assessing novel combinations in non-clear cell RCC with the following take-home points:
- Differential antitumor activity was observed with combination therapies in non clear cell RCC
- Activity was demonstrated across different tumor histologies and both in first line and later lines of therapy
- Response rates and survival with combination therapy in this multicenter dataset remain inferior to rates seen in clear cell RCC
- Further prospective studies are warranted
Presented by: Deepak Kilari, MD, Clinical Cancer Center, Medical College of Wisconsin, Milwaukee, WI
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024.