Editor’s Note: At the 2026 Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO GU 2026), Chinese investigators once again made a strong impact on the international stage. Immunotherapy combined with targeted therapy has become the mainstream treatment paradigm for advanced renal cell carcinoma. However, key clinical questions remain unresolved worldwide, particularly how to optimize treatment strategies after immune-oncology (IO) therapy failure and how to rationally sequence or combine therapies in the era of multiple available agents.At this year’s meeting, the team led by Professor Zhisong He presented a phase II clinical study (Abstract No. 497) investigating treatment options for advanced renal cancer following IO failure, which drew considerable attention. Meanwhile, landmark studies in prostate cancer—including PEACE-3 and KEYNOTE-B15—were also reported, further stimulating discussion on precision combination strategies.
Oncology Frontier invited Professor Zhisong He for an in-depth interview to discuss treatment challenges after immunotherapy failure in advanced renal cancer, the exploratory value of the fruquintinib plus everolimus combination, and evolving strategies for combination and sequential therapy in prostate cancer. His perspectives offer forward-looking insights for clinical practice.
01
This year’s ASCO GU featured many noteworthy studies from China, including your team’s work. In clinical practice, what is currently the most critical factor guiding treatment decisions for patients with clear cell renal cell carcinoma (ccRCC) after failure of immunotherapy? Is it the lack of high-level evidence, the difficulty of stratifying highly heterogeneous patients, or limitations related to toxicity and comorbidities?
Professor Zhisong He: Advanced renal cancer has now fully entered the era of combined targeted therapy and immunotherapy. However, a major challenge remains in clinical practice: globally, there is still a lack of high-level evidence to guide treatment choices after failure of these combination regimens.
As you mentioned, patient heterogeneity and the difficulty of stratification are indeed real issues. After IO failure, clinicians face a particularly challenging question: should the next step be switching to another targeted agent, or should immunotherapy still be continued in some form? Some evidence suggests that switching to a targeted therapy with a different mechanism of action may be more reasonable, but the overall level of evidence remains limited. This represents a significant unmet clinical need.
Another important consideration is identifying the reason for treatment failure. Was it disease progression, or was it intolerance to the therapy? If intolerance is the issue, we must further determine whether the patient cannot tolerate the targeted therapy, the immunotherapy, or both. This is precisely where the challenge of precise patient stratification lies and remains one of the key unresolved issues in clinical practice.
Combination regimens of targeted therapy and immunotherapy are not universally effective. Treatment failure and disease progression are inevitable for some patients, and therefore we must continue exploring more effective subsequent treatment strategies for this population.
02
In your team’s study presented at this meeting (Abstract 497), why did you choose the combination of fruquintinib plus everolimus as a post-IO treatment strategy? Is the primary goal rapid disease control, or achieving longer-term survival benefits?
Professor Zhisong He: The fundamental goal of cancer treatment is always to extend survival while maintaining patients’ quality of life. This aligns closely with the theme of this year’s meeting—patient-centered care and translating clinical research into real-world practice.
Our study is currently at an early exploratory stage. The rationale for investigating fruquintinib, a domestically developed multi-target tyrosine kinase inhibitor (TKI), in combination with everolimus, an mTOR inhibitor, in patients with advanced renal cancer after IO failure is based on several considerations.
First, in the earlier era of targeted therapy alone, the combination of lenvatinib plus everolimus demonstrated favorable efficacy as second-line treatment after failure of targeted therapy. Now that we have entered the era of immunotherapy-based combinations, an important question is whether combinations with similar mechanisms of action can still provide meaningful clinical benefit and potentially further improve outcomes.
Second, fruquintinib is an innovative anti-tumor agent developed in China. By combining it with everolimus, we aim to explore whether this strategy can provide improved survival outcomes for patients who have progressed after IO therapy. Preliminary data also suggest that the safety profile of this combination is manageable.
The initial results from our phase II study presented at this meeting indicate encouraging signals in both efficacy and safety. We plan to continue advancing this research and hope to present more mature data at future international conferences.
03
Based on the current signals of efficacy and safety, can you outline a practical patient profile for this regimen? Which patients might be suitable candidates, and which patients should be approached cautiously? In real-world practice, adverse events such as hypertension are a major concern—how should they be proactively managed?
Professor Zhisong He: Thank you for raising these highly clinically relevant questions. However, as this study is still in an early exploratory phase, including ongoing dose-finding, we are not yet able to clearly define which patient populations are most likely to benefit or to provide precise treatment recommendations.
These are precisely the issues we hope to address in our subsequent analyses. As more patients are enrolled and additional data accumulate, we expect to gain clearer insights into patient selection and optimized clinical use.
04
Looking more broadly at the advances in genitourinary oncology presented at this year’s ASCO GU—such as the PEACE-3 and KEYNOTE-B15 studies—how do you view the value of combination strategies in the future of precision treatment for prostate cancer? What directions should future research take?
Professor Zhisong He: Several landmark studies on combination therapy in prostate cancer were presented at this meeting. Today, the therapeutic landscape for prostate cancer has become increasingly rich and diverse.
Treatment strategies now extend far beyond traditional androgen pathway inhibition. They include PARP inhibitors, targeted therapies related to the PI3K/PTEN signaling pathway, radioligand therapy, and—highlighted at this meeting—multiple antibody–drug conjugates (ADCs). As a result, prostate cancer management now encompasses several major therapeutic pathways.
The key question that arises is how these agents should be used: should therapies targeting different pathways be administered concurrently in combination, or should they be sequenced?
Historically, prostate cancer has already seen the emergence of triple-therapy approaches. With the introduction of newer agents such as PARP inhibitors, additional questions arise. For instance, androgen deprivation therapy combined with a PARP inhibitor has already shown clinical value. Should we further explore four-drug or even five-drug combinations?
Current evidence suggests that combination therapy is not always a simple case of “1 + 1 > 2.” In some situations, the incremental efficacy may be limited, while toxicity may increase substantially—sometimes exceeding the expected additive effects. Therefore, extensive prospective studies are still required to validate these strategies.
The encouraging news is that we now have a much broader range of therapeutic options. The potential combinations and sequences among these drugs are opening an entirely new landscape for prostate cancer treatment. Prostate cancer management has evolved from an era dominated by androgen deprivation, anti-androgen therapy, and chemotherapy to one characterized by multiple drug classes and increasingly precise treatment strategies.
Ultimately, the central goal of future research remains patient-centered: maximizing survival while preserving quality of life. Although much work still lies ahead, the prospects for precision therapy in prostate cancer are becoming increasingly promising.
Professor Zhisong He
