Wenxin (Vincent) Xu, MD, discusses ongoing efforts to identify new biomarkers in metastatic renal cell carcinoma.  

Dr Xu on Ongoing Biomarker Research in Metastatic RCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, discusses ongoing efforts to identify emerging biomarkers in metastatic renal cell carcinoma (RCC).

The ongoing phase 2 OPTIC RCC trial (NCT05361720) is assessing the use of established biologic clusters to guide selection between an immuno-oncology (IO) and TKI approach vs an IO/IO regimen for patients with clear cell RCC, Xu begins. The study utilizes mRNA gene expression signatures derived from prior phase 3 trials like IMmotion151 (NCT02420821) and JAVELIN Renal 101 (NCT02684006), he notes. RNA sequencing will be performed on metastatic tissue samples from newly diagnosed patients with RCC and used to assign tumor clusters. This classification informs treatment selection, as patients with angiogenic clusters will receive a combination of cabozantinib (Cabometyx) and nivolumab (Opdivo), while those with immune inflammatory clusters are treated with ipilimumab (Yervoy) and nivolumab.

Patients are eligible for enrollment on the study if they have not been previously exposed to systemic therapy, including in the neoadjuvant or adjuvant setting, and have at least 1 measurable lesion as defined by RECIST v1.1 criteria. The primary end point of the OPTIC RCC trial is objective response rate. Study investigators hypothesize that using these molecular tumor clusters to guide first-line therapy will result in a 20% higher ORR compared to historical controls from previous unselected trials.

Although OPTIC RCC is a small trial, it represents a shift towards personalized medicine in RCC, Xu states. By leveraging gene expression profiles, OPTIC RCC seeks to identify specific biomarkers that predict response to targeted therapies versus immunotherapies, thereby optimizing treatment decision-making in RCC, Xu adds.

In parallel with the OPTIC RCC trial, there are ongoing efforts across different research groups to investigate circulating biomarkers that could serve as predictors of therapy response, Xu continues. These efforts aim to develop blood-based tests that could streamline treatment selection and monitoring, he explains.

Overall, these initiatives reflect a growing emphasis on biomarker-driven approaches in oncology, offering hope for more tailored and effective treatments for patients with RCC and other cancers, Xu concludes.

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Wenxin (Vincent) Xu, MD, discusses ongoing efforts to identify new biomarkers in metastatic renal cell carcinoma.
 

Dr Xu on Ongoing Research Initiatives in ccRCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, assistant professor, medicine, Harvard Medical School, highlights ongoing research in patients with renal cell carcinoma (RCC), spotlighting significant developments and emerging updates in patients with non–clear cell RCC (ccRCC).

Recent developments in RCC offer promising avenues for improved patient outcomes, Xu begins. Ongoing trials are generating anticipation, particularly large triplet therapy trials exploring the addition of a third medication to the lenvatinib (Lenvima) plus pembrolizumab (Keytruda) regimen, he reports. Initial results from the phase 3 CLEAR trial (NCT02811861) have already demonstrated the efficacy of lenvatinib plus pembrolizumab in patients with advanced RCC, and the inclusion of a CTLA-4 inhibitor, such as quavonlimab (MK-1308), or a HIF-2α inhibitor, such as belzutifan (Welireg), could enhance treatment responses, offering significant benefits for patients, Xu says.

Additionally, the ongoing phase 3 PDIGREE trial (NCT03793166) is investigating the early introduction of cabozantinib (Cabometyx) to first-line ipilimumab (Yervoy)/nivolumab (Opdivo) therapy in patients with stable disease or non-progressive disease, he expands. This research addresses an important clinical question and may further optimize treatment strategies, according to Xu. Furthermore, smaller trials exploring novel treatment approaches, such as CAR T-cell therapies, show promise, with some phase 1 trials reporting positive clinical responses, Xu reports.

In the realm of non-ccRCC management, although progress has been made, challenges persist compared with the successes achieved in ccRCC management, Xu elucidates. Ongoing trials continue to shed light on treatment options. Additionally, phase 2 trials have shown activity with lenvatinib plus pembrolizumab and cabozantinib plus nivolumab across various non-ccRCC histologies, he continues.

Moving forward, there is a growing emphasis on developing targeted therapies tailored to the biological characteristics of non-ccRCC subtypes, Xu emphasizes. Although navigating the management of these rare histologies poses challenges, concerted efforts by researchers are underway to identify promising compounds based on patient biology rather than extrapolation from ccRCC data, Xu says. With ongoing research and collaboration, the outlook for advancements in non-ccRCC treatment appears promising, with more breakthroughs expected in the future, he concludes.

Wenxin (Vincent) Xu, MD, highlights research in renal cell carcinoma, spotlighting developments and updates in patients with non-clear cell disease.

Dr Xu on Treatment Decision-Making in RCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, assistant professor, medicine, Harvard Medical School, discusses treatment decision-making for patients with renal cell carcinoma (RCC), highlighting how he approaches treatment upon disease progression for patients in this population.

At present, treatment decisions for this patient population remain highly individualized, tailored to the specific characteristics of each individual who presents with RCC, Xu begins. There isn't a universal treatment approach that fits every individual patient, he explains, adding that several viable options are available. For example, patients experiencing rapidly progressive disease symptoms who are feeling unwell due to their illness may find benefit from treatment with the combination of an immunotherapy agent and a TKI due to the swift onset of response and high response rates associated with these types of combinations, which may alleviate their symptoms promptly, Xu elucidates.

Conversely, patients with metastatic disease who are experiencing more mild symptoms and desiring a chance at long-lasting response or even treatment-free survival are suitable candidates for ipilimumab (Yervoy) plus nivolumab (Opdivo), as the use of this regimen is backed by extensive durability data, Xu states. The course of treatment progression in this patient cohort varies, with a significant factor being the toxicities encountered during initial treatment, he expands. For instance, patients enduring TKI-associated toxicities over extended periods may find relief in transitioning to belzutifan (Welireg), offering respite from TKI-related adverse effects and potentially improving their quality of life, he elucidates.

On the contrary, patients tolerating TKI toxicities well and demonstrating robustness for further treatment may benefit from aggressive second- or third-line TKI regimens such cabozantinib (Cabometyx) or lenvatinib (Lenvima) plus everolimus (Afinitor), which are known for their continued efficacy, Xu continues. Tivozanib (Fotivda), which is another present TKI option for patients within this population, could be considered for patients who are still responsive to TKI treatment, he says. The overarching objective for many patients is to sequence treatments effectively, maximizing the chances of achieving a favorable response, Xu concludes.

Wenxin (Vincent) Xu, MD, discusses treatment decision-making in patients with renal cell carcinoma.

Wenxin (Vincent) Xu, MD

Articles

Dr Xu on Ongoing Biomarker Research in Metastatic RCC

Dr Xu on Ongoing Research Initiatives in ccRCC

Dr Xu on Treatment Decision-Making in RCC