Dr Xu on Changes in Systemic Therapy in RCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School,provides insights into the rapid evolution of systemic therapy for patients with renal cell carcinoma (RCC), marked by significant developments and emerging treatment modalities.

The emergence of various systemic therapies has quickly altered the RCC treatment paradigm, Xu begins, noting that the most recent change came in December 2023, when the FDA approved belzutifan (Welireg) for the treatment of patients with advanced RCC following a PD-1 or PD-L1 inhibitor and a VEGF TKI, making it the first HIF2A inhibitor approved for patients with refractory kidney cancer. This introduction of a novel therapeutic class offers promise in addressing unmet needs in the treatment of RCC, Xu says.

Furthermore, Xu notes the significance of pembrolizumab (Keytruda) demonstrating efficacy in the adjuvant setting, with the first overall survival benefit demonstrated in this patient population, underscoring a shift in the standard of care, Xu explains.

In the realm of first-line metastatic RCC, ongoing trials evaluating doublet therapies continue to yield promising data, he continues. Recent findings suggest sustained benefits for the various approved combinations over single-agent TKIs, presenting opportunities for optimizing treatment strategies and improving patient outcomes, Xu notes.

Xu highlights the imperative need for biomarkers in guiding treatment decisions for RCC. Although the field has made progress through the combination of highly active agents, results from the phase 3 COSMIC-313 trial (NCT03937219), which evaluated the triplet of cabozantinib (Cabometyx), nivolumab (Opdivo), and ipilimumab (Yervoy), revealed potential limitations associated with indiscriminate combination therapy. Despite improved progression-free survival observed with the triplet in this study, significant toxicity underscores the necessity for more refined combination strategies tailored to individual patient profiles, Xu says.

Several trials are of interest in exploring biomarkers for predicting treatment response in RCC, he continues. One such trial focuses on mRNA gene expression signatures derived from prior phase 3 trials, aiming to differentiate patients more likely to respond to anti-VEGF therapy vs immunotherapy. Additionally, investigational biomarkers, including circulating biomarkers, hold the potential for informing treatment decisions and optimizing therapeutic outcomes, Xu says.

Xu emphasizes the importance of advancing precision medicine in RCC management through the integration of biomarkers into treatment algorithms. Continued research efforts are warranted to elucidate the utility of biomarkers in guiding treatment selection and optimizing therapeutic efficacy for patients with RCC, he concludes.