Exciting New Treatment Updates Are on the Horizon for Advanced RCC

Moshe Ornstein, MD, MA

Medical Oncologist

Cleveland Clinic

As part of an Around the Practice program hosted by CancerNetwork®, Ornstein spoke about frontline treatment strategies and managing toxicities associated with these therapies in patients with advanced renal cell carcinoma (RCC). Additionally, he discussed how he stays informed of the latest advances in the RCC space by attending relevant conferences and reading journal coverage.

Beyond the currently prominent treatment modalities and methods for mitigating toxicity in patients, Ornstein highlighted a need to further research biomarkers to help select therapies more optimally for this population. He also stated that he was looking forward to progress and development in novel treatments, which may include the use of chimeric antigen receptor (CAR) T-cell therapies and antibody-drug conjugates for advanced RCC.

“There’s been tremendous progress in advanced RCC management, but there’s still a long way to go,” Ornstein said.

Q / Given the rapidly evolving therapeutic landscape, how do you stay up to date on the latest clinical trial results and treatment options for advanced RCC?

Ornstein / The therapeutic landscape for the treatment of patients with advanced RCC is changing incredibly rapidly. Just in the [past] handful of years, there have been multiple new combinations. For patients with treatment-naive advanced RCC, it’s important to stay on top of these data to provide optimal outcomes for our patients. The way I stay on top of data is by attending meetings and reading journals, whether it’s the pure academic journals or the journals that come through the mail. It is important to stay on top of the new treatment options as well as how to manage the adverse effects [AEs] of those treatments to help optimize a patient’s quality and quantity of life.

Q / For patients with specific comorbidities or treatment resistance, what are some promising personalized or targeted therapy approaches in advanced RCC?

Ornstein / Patients with advanced RCC are a heterogeneous patient population. Many of them are going to be in their 60s or 70s and have a variety of comorbidities. When we’re taking care of these patients, we need to consider hypertension, other vascular concerns, gastrointestinal issues, and any comorbidities that might impact treatment choice or how we manage for that patient to stay on therapy for as long as possible. Keeping those comorbidities in mind is important. Some of these patients who are on therapy, even with therapies that have response rates as high as 60% to 70%, will develop treatment resistance [at some point]. For those patients, it’s important to know not [only] what the frontline therapy is with the incredible advances of immunotherapy-based combinations, but also what those refractory lines of treatment are for the patients whose cancer progresses beyond an immunotherapy-based combination.

Q / What are some of the biggest challenges you have in managing the AEs and toxicities associated with advanced RCC treatment?

Ornstein / Although the treatment changes for advanced RCC with immunotherapy-based combinations in the frontline [setting] have improved response rates, progression-free survival, and overall survival compared with historical standards, at the end of the day, some of these patients are going to have AEs from treatment. The biggest challenge when it comes to managing the AEs is those AEs can be from either an immunotherapy or from the immunotherapy partner, the tyrosine kinase inhibitor [TKI]. For instance, fatigue, diarrhea, and elevated liver tests can be from immunotherapy or targeted therapy. Developing a strategy to determine which agent is responsible for that AE is critical in terms of managing the AE, [as well as] knowing which agent a patient can stay on and when and [whether] we can resume the therapy that was on hold while the toxicity was being managed.

Q / Looking toward the future, how do you hope to see the field of RCC evolve?

Ornstein / There’s been tremendous progress in advanced RCC management, but there’s still a long way to go. We don’t have any biomarkers to help us select which patient is going to get what therapy, and I’d love to see clinical trials and scientific advancements that help give us either a tissue-based biomarker or a blood-based biomarker to determine which patients should get which therapy. Beyond that, for the [past] decade or so, we’ve been focused on immunotherapy with checkpoint inhibitors and targeted therapy with VEGFR TKIs. We’re looking forward to the field progressing and producing novel therapies—whether they are agents like HIF2α inhibitors, cellular therapies like CAR T-cell therapies, antibody-drug conjugates, or CDK4/6 inhibitors. It’s exciting to see that, despite the advances that have been made, there’s still a lot to come.