Robert A. Figlin, MD
The pharmacologic treatment for advanced renal cell carcinoma (RCC) has evolved considerably since the FDA approved interleukin-2 as the first systemic therapy for the tumor type in 1992.1
The next drug the agency approved was sorafenib (Nexavar), which was the first targeted therapy for RCC. Since then, the FDA has approved more than 20 drugs for RCC in the past 12 years. At a recent OncLive®
, a panel of experts in genitourinary malignancies talked about how the treatment paradigm for patients with advanced RCC has changed and is likely to continue changing.
Robert A. Figlin, MD, who moderated the Peer Exchange® panel, said the rapid pace of drug approvals for RCC leaves oncologists with many unanswered questions about the optimal way to use the new agents. The panelists reviewed data from clinical trials that can help guide treatment decisions for the first-line setting and beyond.
“New data continue to emerge to help us navigate a pathway for each individual patient, often through multiple lines of therapy,” Figlin said. The basic goal of treatment remains the same: find a way to cure the patient’s cancer while preserving the quality of life. Panelist Eric Jonasch, MD, suggested progress is being made on that front, with the recent approval of immunooncology agents that prolong overall survival (OS) and even cure RCC in a subset of patients.
As the number of available drugs has grown, the patient population with RCC also has changed, Figlin observed. Toni K. Choueiri, MD, agreed and noted that they are now seeing a growing population of patients who had progression on multiple lines of therapy, including immunooncology drugs. Figlin expressed concern that some clinicians might be discontinuing traditional VEGF-targeted tyrosine kinase inhibitors (TKIs) too quickly—that instead of using dose adjustments to manage tolerance issues, there is a rush to switch patients to immuno-oncology drugs.
Choueiri said when the TKIs were first introduced, the treatments were quickly discontinued due to adverse events (AEs). As clinicians learned to manage the AEs of TKIs, however, patients could continue taking the drugs until their disease progressed. “I have to be honest with you, I see the movement going back to where we were—with the patient being taken off quickly from agents like sunitinib or pazopanib [Votrient] who sometimes could have stayed on the drug for a longer period of time, had the side effect been managed in a different way,” Choueiri said.
Michael R. Harrison, MD, said decisions about what therapy to use or when to discontinue a therapy should consider the patient’s goals of care. “If you ask patients what is their goal, different patients have a different balance between prioritizing qualify of life versus tumor response variables or outcomes,” he said.
One of the emerging debates concerns when to start treatment. Figlin said, “Over the years, everybody thought ‘once you find [RCC], you treat it.’ And we’re learning now that may not be necessary. There are some patients whom we can observe, which is different than a decade ago.” He asked the panelists what they thought about the concept of active surveillance after nephrectomy in patients with slow-growing disease.
“We do have data at this point in time that suggests it’s probably safe to wait, especially if you have an individual who has perhaps a small number of lesions, who has slowly growing disease, who has excellent performance status,” said Jonasch. “This is a strategy that I certainly employ with some of my patients,” he added.
David I. Quinn, MBBS, PhD, pointed to data from a phase II trial published in 2016 that showed active surveillance was a successful approach for a subset of patients with metastatic RCC.2
“What was clear was that patients who were particularly good risk or intermediate risk based on Motzer or Heng criteria could do well, especially if they had pulmonary metastases as their major site of disease,” he said.