Non–Clear Cell RCC Subtypes Require Individualized Approach to Treatment Selection

Jaime R. Merchán, MD

When evaluating patients with less common non–clear cell renal cell carcinoma (ccRCC), it is critical to identify histological subtype, perform genomic profiling, and have knowledge of currently enrolling clinical trials or accepted therapies to ensure that patients are directed toward the optimal treatment approach, according to Jaime R. Merchán, MD.

In the interview with OncLive^®, Merchán spotlighted case studies on patients with rare non-ccRCC histologies, discussing their clinical presentation, recent data on immunotherapy and targeted treatment options for the management of these disease subtypes, and patient outcomes on these therapies.

“What [these case studies] teach us is that every case of RCC is different—especially in non-ccRCC,” Merchán said following his participation in an OncLive® State of the Science Summit on genitourinary cancers. Merchán is an associate professor in the Department of Medicine, Division of Medical Oncology; co-leader of the Translational and Clinical Oncology Research Program; and director of the Phase 1 Clinical Trials Program at Sylvester Comprehensive Cancer Center, part of the University of Miami Health System in Florida.

OncLive: Could you briefly outline the first patient case study that was presented during the meeting. How did they present, and what factors informed treatment decision making?

Merchán: The first case that I presented was a patient with papillary type 1 RCC who had a resection of the primary tumor after definitive therapy and then recurred. He had multiple metastases, both in the mediastinum and in the retroperitoneal lymph nodes. We went over the steps that a medical oncologist in kidney cancer considers in order to evaluate a patient, to select the best treatment, and to determine which risk category the patient belongs to.

Then, we had a discussion on the most recent data in terms of systemic therapy options and their efficacy in non-ccRCC. Based on the National Comprehensive Cancer Network, the preferred regimens for advanced non-ccRCC are either enrollment into clinical trials or a single-agent TKI like cabozantinib [Cabometyx]. However, new data are coming [down the pike on] IO/TKI combinations in this space, including cabozantinib and nivolumab [Opdivo] and lenvatinib [Lenvima] plus pembrolizumab [Keytruda]. Data from [the latter study, KEYNOTE-B61 (NCT04704219)] were recently published in Lancet Oncology. The trial [included] about 158 patients who were given pembrolizumab plus lenvatinib at standard doses in the first line. This regimen was associated with an [approximate] 49% response rate and an 18-month median progression-free survival, which are, by any accounts, outstanding and promising numbers.

What was learned from your second case study, and why was it important to present?

The second case that I presented was on a very rare form of non-ccRCC, which is called hereditary leiomyomatosis and renal cell cancer [HLRCC]. This is a hereditary autosomal-dominant cancer associated with papillary RCC, non-type 1 papillary RCC, and other tumors like a leiomyoma of the uterus. This is caused by a germline mutation of a gene [producing the enzyme] fumarate hydratase, which is important in the Krebs cycle. We talked a bit about the disease, [including] how rare but how important it is to recognize it, because this usually occurs in younger patients, females more than males. It seems to be an aggressive form of non-ccRCC.

We also went over some of the limited data from small studies showing the activity of several regimens in this disease, because it is such a rare type of kidney cancer. We specifically talked about one regimen that has been developed by the National Cancer Institute: erlotinib [Tarceva] and bevacizumab [Avastin], which has been associated with high response rates in this rare form of RCC.

Overall, what do these case studies convey about the heterogeneity of non-ccRCC?

These cases are good examples. It is important to understand what histological type we’re talking about and the clinical setting, because hereditary RCC can [sometimes] be treated with targeted therapies. Other [cancers that] are not hereditary can be treated with combination therapies that have been either approved or show promising results. What I tell many patients or colleagues is that non-ccRCC is so heterogeneous that treatments need to be individualized. Genomic profiling may help, especially to determine whether there is a targetable mutation. Finally, it is extremely important to always consider a clinical trial for patients with non-ccRCC.