Robert A. Figlin, MD
Historically, patients with advanced renal cell carcinoma (RCC) have had few treatment options, but several targeted agents and one immunotherapy, the checkpoint inhibitor nivolumab, have been approved within the past 5 years, considerably expanding the RCC treatment arsenal. In the frontline setting, targeted agents are often the go-to therapy.
Options include vascular endothelial growth factor (VEGF) inhibitors, an anti-VEGF monoclonal antibody, and mammalian target of rapamycin (mTOR) inhibitors (Table). Selecting from these treatments remains a challenge because guidelines on optimizing their use are still lacking.
During a recent OncLive
Peer Exchange panel titled “Sequencing Therapies in Advanced Renal Cell Carcinoma” and moderated by Robert A. Figlin, MD, the panelists discussed the complexity of caring for patients with advanced RCC and described their frontline treatment approach, including when to start treatment, which agents they use, and when treatment needs to be switched.
Although it is clear that considerable work still needs to be done on the RCC treatment front, there is also much to look forward to as studies continue to assess new treatment options and combination strategies, define optimal sequencing of treatments, and identify predictive biomarkers to improve treatment decision making.
To Treat or Not to Treat?
A key question that arises following a diagnosis of advanced RCC is when to start systemic treatment. Although most oncologists and patients want to start treatment immediately, a recently published phase II trial found that a small subset of patients might benefit from a period of active surveillance.1
“It’s about 10% of patients who can get away without [immediate] treatment,” said Elizabeth R. Plimack, MD, MS, who was one of the study’s lead investigators. She noted that patients with stable disease or slowly progressing disease might be good candidates for this approach, provided they are asymptomatic and otherwise healthy.
Daniel J. George, MD
“If you have patients who are symptomatic or have a lesion threatening a critical structure or organ, those are the people you’re going to want to start sooner,” she said. Daniel J. George, MD, added that patients with low-disease volume could also be considered for active surveillance.
Even when candidacy for active surveillance is clearly established, the panelists noted that getting patients onboard with this approach can be a challenge. “When patients get to you, they’re often anxious and motivated to do something,” said David F. McDermott, MD.
Patients might fear that they would miss out on the benfits of therapy if their cancer is not treated immediately, despite no evidence indicating that. McDermott said many patients will consider active surveillance after he explains that therapies usually stop working at some point and that “the sooner we start, the sooner we get to the point where we’re going to need to do something else.”
Which Agent to Choose?
When deciding on a treatment approach, important considerations that can help personalize treatments include patient goals, clinical trial evidence, and patient characteristics, said Thomas Hutson, DO, PharmD.
Thomas Hutson, DO, PharmD
He noted the importance of the NCCN Guidelines in further guiding treatment and ensuring treatment paradigms are followed. “There have been drugs that have been approved in particular settings, so if we’re starting off with initial therapy and we make the decision we’re not going to delay treatment in a patient, I think that’s important to consider,” he said.
When systemic treatment is needed, frontline options include cytokine therapy with high-dose interleukin-2 (IL-2), which was the only systemic treatment option for metastatic RCC until late 2005, or a targeted therapy.2
Patients can also be enrolled into a clinical trial.