More than 3,700 papers on kidney cancer were published in 2014 but none offered major changes in the therapeutic landscape for metastatic renal cell cancers (mRCCs), reported Toni K. Choueiri, MD, Director of the Kidney Cancer Center, and Clinical Director of The Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, MA.

“If you look at the NCCN guidelines that were just updated, version 3.2015, there is not a major change,” he said.¹ “But there are a lot of trials that provide important insights for future trials and management of patients.”

Dr. Choueiri delivered the 2014 Year in Review research retrospective at the 2015 Genitourinary Cancers Symposium.

Among advances he reviewed were clinical trials comparing approved targeted agents, health outcomes research, and biomarkers. “A lot of work also remains to be done in non-clear cell RCC,” he emphasized.

Comparing Approved Targeted Therapies

Dr. Choueiri reviewed three important papers from 2014 that compared approved targeted agents: an updated report on overall survival from the COMPARZ trial,² comparing sunitinib versus pazopanib in patients previously untreated; the INTORSECT trial comparing temsirolimus versus sorafenib after sunitinib therapy³; and RECORD-3, a clinical trial comparing sunitinib versus everolimus.⁴

“There was an updated report from the COMPARZ trial that showed pazopanib is not inferior to sunitinib in the front-line setting,” Dr. Choueiri said. “Why is this important? Because it provides a benchmark for future trials of single-agent, targeted therapy that utilize pazopanib or sunitinib as a control arm.”

Another extremely important trial published in 2014 was the INTORSECT trial, Dr. Choueiri said. “As we know, second-line agents after progression of [vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKIs)] is an open field.”

Progression-free survival (PFS) was this INTORSECT study's primary endpoint, and median PFS did not vary significantly between temsirolimus and sorafenib, he noted.

“But to our surprise in the RCC community, the secondary endpoint—overall survival—did favor sorafenib,” Dr. Choueiri said. “I'm personally still puzzled by that result. It could be that sorafenib results in higher survival,” but uncertainties remain, he said.

“If you dig and look at patient characteristics, [overall survival] was not different between the study arms. If you look at receipt of third-line therapy after progression, it's not different. If we look at the patient that came off therapy because of treatment discontinuation, it's not different. This is important to remember.”

Finally, the phase 2 RECORD-3 study tested the standard sequence of sunitinib followed by everolimus. And everolimus followed by sunitinib. The data show that everolimus first is inferior to the standard (sunitinib first) treatment sequence.

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