ASCO GU 2020: Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma

San Francisco, CA ( Renal cell carcinoma represents a heterogeneous cancer including multiple subtypes. The last few years have been punctuated by the development of multiple new treatment options with clinicians having little tools in way of patient selection. While pathologic evaluation traditionally has allowed for classification, genomic subtyping represents a novel approach for better characterizing this disease in order to better match patient to treatment.

Kyrollis Attalla was invited to report on his team’s experience with next-generation sequencing. The study aimed to characterize the prevalence and genomic landscape of actionable genomic alterations in renal cell carcinoma (RCC). Actionable alterations with clinical or biologic evidence supporting an association with response to targeted therapy were stratified by level of evidence using an oncology knowledge database (OncoKB, work flow shown below).

ASCO GU 2020 OncoKB workflow

The team evaluated data from 35,668 patients, which was subsequently narrowed to include the 15 cancer types with the highest prevalence of actionable alterations. RCC was ranked 13th in prevalence of actionable alterations. 708 RCC samples were included in their cohort, 259 and 449 metastatic and primary samples, respectively. Although 69% of patients with RCC harbored at least one known oncogenic mutation, only 13 percent (90/687) harbored alterations for which compelling clinical data currently exist to justify the use of a standard or an investigational agent (levels of evidence 1 to 3B).

ASCO GU 2020 alterations in RCC

Furthermore, the most common histologic subtype, clear cell RCC, harbored the vast majority of actionable alterations (52/421; 12%). Additionally, the type of alternation varied by the histologic subtype with clear cell RCC demonstrating more somatic mutations, while papillary RCC demonstrated more copy number variations.

This talk, highlighted the potential role of genetic testing in identifying candidates for targeted therapy. Future studies are needed to validate these preliminary results and to further elucidate the role of genetic testing on informing treatment decisions.

Presented by: Kyrollis Attalla, MD, Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center, New York City, NY

Written by: Adrien Bernstein, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Fox Chase Cancer Center, Philadelphia, PA at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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