Systemic treatment for metastatic renal cell carcinoma (mRCC) is evolving rapidly in the era of targeted therapy and immunotherapy combinations, bringing two major clinical questions to the forefront.First, second-line immunotherapy–TKI combination studies, represented by FRUSICA-2, primarily enrolled patients whose disease had progressed on or who were intolerant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and who had not previously received immunotherapy. As immunotherapy–TKI combinations and dual immunotherapy regimens increasingly become mainstream first-line options, it is essential to clarify whether these second-line findings can be extrapolated to patients previously treated with immunotherapy.
Second, no head-to-head comparisons are currently available between the dual immunotherapy regimen of nivolumab plus ipilimumab and immunotherapy–TKI combinations consisting of a PD-1 inhibitor plus a VEGFR-TKI in the first-line setting. How to individualize treatment based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk stratification, tumor burden, disease progression rate, the need for rapid tumor shrinkage, and patient comorbidities remains a subject of considerable debate.
In this issue of Getting to the Bottom of the Debate, Professor Xuewen Jiang of Qilu Hospital of Shandong University and Professor Hailiang Zhang of Huadong Hospital, Fudan University engage in a structured debate on these two key questions.
Debate Topic 1
Extrapolating Second-Line Evidence: Can the FRUSICA-2 Results Be Extrapolated to Patients Previously Treated with Immunotherapy?
The key evidence supporting second-line immunotherapy–TKI combination therapy, such as fruquintinib plus sintilimab, comes primarily from patients whose disease progressed on or who were intolerant to first-line VEGFR-TKI therapy and who had not previously received immunotherapy.
Can these findings be directly extrapolated to patients previously treated with immunotherapy, including those who received first-line immunotherapy–TKI combinations or dual immunotherapy? How should clinicians identify patients most likely to benefit by considering primary or acquired resistance, prior TKI intolerance, IMDC risk stratification, sarcomatoid differentiation, and tumor burden?
Opening Statements
Affirmative Side | Cautious Extrapolation Is Possible, and Immunotherapy Rechallenge Strategies Such as the “Happy Combination” May Also Be Considered in Previously Immunotherapy-Treated Patients
Professor Xuewen Jiang
Qilu Hospital of Shandong University
My position is that this evidence can be cautiously extrapolated, and that small-scale exploratory studies and clinical trials in patients previously treated with immunotherapy are also justified.
Looking at the FRUSICA-2 study design, patient enrollment was completed at a time when immunotherapy–TKI combinations had not yet become the mainstream first-line approach. In particular, patients in the favorable-risk group had not yet routinely received first-line immunotherapy. As a result, the study population consisted primarily of patients whose disease had progressed after first-line TKI therapy.
In recent years, immunotherapy–TKI combinations have become increasingly widespread. At present, apart from the CSCO guidelines, which retain TKI monotherapy as a first-line option for favorable-risk patients, most patients without contraindications to immunotherapy receive an immunotherapy–TKI combination as first-line treatment.
After failure of first-line immunotherapy–TKI combinations or dual immunotherapy, most of the available evidence still comes from patients who experienced TKI failure and had not previously received immunotherapy. In clinical practice, second-line options mainly include fruquintinib or regimens such as lenvatinib plus everolimus. At the same time, some studies support immunotherapy rechallenge. For example, pembrolizumab plus lenvatinib, commonly referred to in China as the “Coke combination,” has achieved encouraging progression-free survival (PFS) results.
Fruquintinib is a highly selective inhibitor of VEGFR-1, VEGFR-2, and VEGFR-3, with a relatively favorable adverse-event profile. In FRUSICA-2, fruquintinib plus sintilimab achieved an impressive PFS of more than 20 months, while fruquintinib monotherapy also achieved a PFS of more than 10 months.
Therefore, for patients previously treated with immunotherapy, rechallenge with sintilimab plus fruquintinib, commonly referred to in the field as the “Happy combination,” is a strategy worth exploring.
These are my preliminary views.
Negative Side | The Evidence Is Strictly Limited to Patients with TKI Failure Who Are Immunotherapy-Naive; Extrapolation Must Respect the Boundaries of Evidence-Based Medicine
Professor Hailiang Zhang
Huadong Hospital, Fudan University
I am very pleased to join Professor Xuewen Jiang in this distinctive debate session. Professor Jiang believes that second-line data can be extended to patients previously treated with immunotherapy, or at least that this approach is worth trying. I would like to begin by revisiting the study design.
I was involved in part of this study, led by Professor Dingwei Ye, and also recommended several patients for enrollment. The overall efficacy was indeed impressive: PFS exceeded 20 months, the objective response rate (ORR) was very high—even higher than the ORR reported in some current first-line regimens—and tolerability was relatively favorable.
These results were largely attributable to the characteristics of the two agents. Fruquintinib is a VEGFR-targeted inhibitor with a mechanism similar to that of axitinib. Sintilimab has been widely used in China for various other tumor types, with multiple approved indications, but data in renal cell carcinoma had been lacking. This study therefore filled an important evidence gap regarding its use in advanced renal cancer.
However, we must recognize that the study enrolled patients whose disease had failed to respond to TKI treatment. Their prior therapies were primarily sunitinib and pazopanib, which had been discontinued either because of disease progression or because patients could not tolerate treatment.
Both agents are associated with notable adverse effects. Sunitinib, when administered at the conventional dose of 50 mg daily on a 4-weeks-on, 2-weeks-off schedule, can cause substantial toxicity, making it difficult for many patients to continue treatment. Pazopanib also has toxicities, particularly hepatotoxicity. It is estimated that approximately one-third of patients require dose reduction or treatment discontinuation. Consequently, its overall efficacy in the Chinese population may be somewhat attenuated.
Whether we refer to clinical guidelines, expert consensus, or drug prescribing information, clinical use must remain closely aligned with the populations enrolled in clinical trials. The “Happy combination” is most directly applicable to patients whose disease has progressed on or who are intolerant to sunitinib or pazopanib. Conversely, as first-line immunotherapy–TKI combinations become increasingly widespread, this patient population is likely to become progressively smaller in clinical practice in China.
As for whether immunotherapy-based combinations can be reused after failure of prior immunotherapy, this remains an open question. Some studies have reported encouraging results. For example, an overseas Phase II study of the “Coke combination” after immunotherapy failure reported an ORR of nearly 51%, while several immunotherapy rechallenge studies have reported PFS of approximately 6–9 months.
However, the current standard options after immunotherapy failure are TKI monotherapy or TKI-based combinations, such as cabozantinib and combinations of a TKI with the HIF-2α inhibitor belzutifan. In the absence of head-to-head comparisons, the “Happy combination” may not necessarily offer an advantage over these regimens. After all, these patients have already experienced immunotherapy intolerance or treatment failure, and the incremental benefit of reintroducing immunotherapy may be limited.
That said, from the perspectives of cost-effectiveness and drug accessibility, trying an immunotherapy–TKI combination may still be a reasonable option in selected circumstances.
Exchange 1
Which Findings Can Be Applied to Immunotherapy-Naive and Previously Immunotherapy-Treated Patients, and Which Require Validation in Dedicated Studies?
Professor Xuewen Jiang
Qilu Hospital of Shandong University
Thank you, Moderator.
Our earlier discussion focused on patients previously treated with immunotherapy. For immunotherapy-naive patients, the currently approved indication for this regimen is after failure of first-line TKI therapy. If it is used in immunotherapy-naive patients outside this setting, the supporting evidence remains at the Phase II clinical trial level, and it is not equivalent to the current standard immunotherapy-based combination regimens. At least under the current medical insurance framework, reimbursement is not available for this use.
However, the clinical data are encouraging. After TKI failure, patients’ general condition may deteriorate and their IMDC risk scores often increase. New lesions may also emerge following disease progression. Despite these challenges, FRUSICA-2 achieved a PFS of approximately 22.2 months in this patient population.
When compared indirectly with first-line immunotherapy–TKI studies such as KEYNOTE-426 and CLEAR (the “Coke combination”), these results remain competitive.
Based on these findings, I believe that immunotherapy-naive patients may achieve favorable outcomes with this regimen, whether it is used in the first-line setting or after treatment failure.
Exchange 2
Should Second-Line Treatment Decisions Differ Between Patients with TKI Intolerance and Those with Confirmed Disease Progression? How Should Prior Adverse Events Influence Drug Selection and Dose Adjustment?
Professor Hailiang Zhang
Huadong Hospital, Fudan University
These two patient populations should indeed be managed differently, and prior adverse events will inevitably influence subsequent drug selection and dose adjustments.
First, patients with disease progression (treatment failure) have already developed a certain degree of resistance to TKIs. There is substantial evidence on sequential TKI treatment—for example, switching from sorafenib to pazopanib, from sorafenib to axitinib, or from axitinib back to sorafenib. We have studied these treatment sequences, and overall, PFS tends to shorten with each successive line of TKI therapy. Outcomes are clearly inferior to those achieved in the first-line setting.
For this population, simply switching to another TKI is not a viable strategy. The advantage of the FRUSICA-2 combination is that these patients were still immunotherapy-naive. By combining a TKI with immunotherapy, the impact of TKI resistance may be partially offset, while the therapeutic effects of immunotherapy can also be realized.
Second, patients who discontinue treatment because of TKI intolerance generally have very short treatment exposure. Most receive treatment for only one to two months before stopping because they cannot tolerate it. Their clinical status is therefore closer to that of a treatment-naive population, and they may remain sensitive to TKIs. Their problem is not necessarily resistance to the entire drug class, but rather intolerance to a particular TKI. If they switch to another TKI with a more favorable adverse-event profile, treatment may still be effective.
Therefore, the overall efficacy of TKI plus immunotherapy in this population would be expected to be better than in patients with TKI resistance, potentially resulting in longer PFS and a higher ORR.
Unfortunately, FRUSICA-2 did not conduct a corresponding analysis of these two patient groups. Further subgroup comparisons would be valuable to determine whether meaningful differences exist between them.
Exchange 3
If the Evidence Cannot Be Directly Extrapolated, What Alternative Treatment Approaches Are Currently Acceptable? Which Patient Comparisons and Clinical Endpoints Most Urgently Require Further Investigation?
Professor Xuewen Jiang
Qilu Hospital of Shandong University
Currently, after failure of first-line immunotherapy–TKI combination therapy, second-line treatment still primarily relies on combination regimens. Commonly used and relatively established options include a TKI combined with an mTOR inhibitor, such as everolimus, or a TKI combined with a HIF-2α inhibitor.
Regarding immunotherapy rechallenge, only a small number of studies have reported positive results, while most have failed to demonstrate satisfactory outcomes.
Other novel treatment approaches may also be explored. For example, cadonilimab and Qilu Pharmaceutical’s iparomlimab/tuvonralimab (QL1706, brand name Qibeian), which are PD-1/CTLA-4 bispecific or combination antibodies, could be investigated in combination with small-molecule TKIs. These approaches may provide potential research options for patients previously treated with immunotherapy in the second-line setting. However, few of these strategies are currently supported by large Phase III trials, and most remain at the Phase I or II stage.
Therefore, second-line treatment after failure of first-line immunotherapy–TKI combinations continues to present considerable challenges. The choice of treatment regimen and therapeutic approach must ultimately be individualized according to each patient’s general condition and first-line treatment history, with careful consideration of the most appropriate second-line strategy.
Round Summary
Areas of Agreement
Both professors agree that fruquintinib plus sintilimab (the “Happy combination”), as validated in FRUSICA-2, has demonstrated established efficacy and favorable tolerability, making it an important second-line option for patients with TKI failure or intolerance who are immunotherapy-naive.
For patients previously treated with immunotherapy, evidence supporting immunotherapy rechallenge is primarily based on Phase II studies. Clinical decisions should be individualized according to IMDC risk stratification, resistance mechanisms, tumor burden, and the first-line treatment regimen.
Areas of Divergence
Professor Xuewen Jiang believes that, given the PFS of approximately 22.2 months and the high selectivity and relatively low toxicity of fruquintinib, the “Happy combination” and immunotherapy rechallenge may be cautiously extrapolated to patients previously treated with immunotherapy.
Professor Hailiang Zhang, by contrast, emphasizes the boundaries of evidence-based medicine. The pivotal evidence was derived strictly from patients whose disease had failed to respond to or who were intolerant to sunitinib or pazopanib. After immunotherapy failure, PFS with immunotherapy rechallenge is generally around 6–9 months. Compared with established treatment options such as cabozantinib or a TKI combined with a HIF-2α inhibitor, the “Happy combination” still lacks head-to-head evidence. He also recommends further subgroup analyses comparing patients with treatment failure and those with drug intolerance.
Debate Topic 2
First-Line Treatment Selection: How Can Dual Immunotherapy and Immunotherapy–TKI Combinations Be Individualized?
In the absence of head-to-head studies comparing different immunotherapy-based combination regimens, how should clinicians choose between dual immunotherapy with nivolumab plus ipilimumab and an immunotherapy–TKI combination consisting of a PD-1 inhibitor plus a VEGFR-TKI?
How should this decision be individualized according to IMDC risk stratification, tumor burden, disease progression rate, the need for rapid tumor shrinkage, and patient comorbidities?
Opening Statements
Affirmative Side | Dual Immunotherapy Offers Patients with Advanced Clear Cell Renal Cell Carcinoma the Possibility of Long-Term Survival and Even a Chance of “Cure”
Professor Hailiang Zhang
Huadong Hospital, Fudan University
This is a broad topic, so I will focus on the advantages of dual immunotherapy, and I will invite Professor Jiang to discuss the advantages of immunotherapy–TKI combinations later.
Dual immunotherapy refers to the combination of two immunotherapeutic agents. The most extensively studied approach is the combination of a PD-1 inhibitor and a CTLA-4 inhibitor, although combinations of PD-L1 and CTLA-4 inhibitors have also been explored.
In China, the main dual immunotherapy regimen is nivolumab plus ipilimumab. Other approaches include bispecific antibodies that incorporate both PD-1 and CTLA-4 targets into a single molecule, as well as combination antibodies that package two antibodies in a fixed ratio within a single formulation. One example is Qilu Pharmaceutical’s iparomlimab/tuvonralimab (QL1706, brand name Qibeian).
The overall efficacy of dual immunotherapy is substantial. Take the CheckMate 214 trial as an example. Compared with sunitinib, dual immunotherapy demonstrated significant PFS and overall survival (OS) benefits from the outset in patients with intermediate- and poor-risk disease. In the favorable-risk population, sunitinib initially showed a trend toward better PFS and OS. However, with longer follow-up, the OS curves crossed, and the 6- and 8-year data showed that the OS rate in the dual immunotherapy group had reached approximately twice that in the sunitinib group.
It is important to note that this evidence applies to advanced clear cell renal cell carcinoma (ccRCC); CheckMate 214 did not enroll patients with non-clear cell renal cell carcinoma.
For patients with advanced ccRCC, dual immunotherapy may enable more patients to achieve long-term survival and, in some cases, potentially a cure. Its benefit is not merely temporary disease control but the possibility of changing the overall survival trajectory and offering patients renewed hope.
Nevertheless, the adverse effects of dual immunotherapy are also substantial. Its use in urology remains uncommon. In the past, clinicians were extremely reluctant to use the standard ipilimumab dose of 3 mg/kg. After reducing the dose to 1 mg/kg, some patients could be cautiously considered for treatment in later-line settings, but first-line use remains rare.
At present, dual immunotherapy is used primarily in medical oncology. For example, the team led by Professor Jun Guo at Peking University Cancer Hospital has relatively extensive experience with this approach. Even patients enrolled in clinical trials require close and rigorous follow-up, with no room for lapses in monitoring.
Negative Side | As a VEGF-Enriched Tumor, Renal Cell Carcinoma Has Practical Advantages with Immunotherapy–TKI Combinations in Terms of Toxicity, Accessibility, and Guideline Recommendations
Professor Xuewen Jiang
Qilu Hospital of Shandong University
Professor Hailiang Zhang has just outlined the advantages of dual immunotherapy, particularly the overall survival (OS) benefit observed in patients with favorable-risk disease after 8–9 years of follow-up. However, I would first like to emphasize the potential toxicities. During the CheckMate 214 trial, I heard the team of Professor Zhisong He at Peking University First Hospital describe a case in which a patient experienced a dramatic drop in white blood cell count after receiving ipilimumab. This risk should not be underestimated. For this reason, I remain cautious about the clinical use of ipilimumab and have not yet routinely explored or adopted it in my own practice.
We have participated in the Phase I clinical trial of QL1706 (Qibeian), a combination antibody, and conducted related toxicity assessments. We have also gained experience with other bispecific or combination antibody agents, such as cadonilimab. Overall, the efficacy has been acceptable.
Nevertheless, renal cell carcinoma (RCC) is a VEGF-enriched tumor characterized predominantly by angiogenesis. The advantage of tyrosine kinase inhibitors (TKIs) lies in their ability to target newly formed blood vessels. A preclinical study showed that tumors had abundant vasculature before treatment. After just two days of treatment, the number of blood vessels decreased by more than 60%, and by day seven, newly formed blood vessels had virtually disappeared, resulting in substantial tumor control.
Immunotherapy–TKI combinations not only enhance the antiangiogenic effects of targeted agents but also activate immune cells, including CD8-positive T cells and natural killer (NK) cells, which further attack tumor cells. The favorable responses to immunotherapy observed in RCC, melanoma, and other tumors are partly attributable to this mechanism.
Most large contemporary clinical trials have focused on immunotherapy–TKI combinations, whereas only a limited number of studies, such as CheckMate 214, have investigated dual immunotherapy. Based on long-term outcomes, and considering the overall toxicity profile, drug accessibility, and first-line recommendations in major clinical guidelines, immunotherapy–TKI combinations currently offer more practical advantages across favorable-, intermediate-, and poor-risk populations, including patients at extremely high risk with sarcomatoid differentiation.
Ipilimumab remains subject to limitations in terms of approved indications and insurance coverage in China. Dual immunotherapy is also a recommended treatment option, but given current drug accessibility, immunotherapy–TKI combinations are more readily accessible in clinical practice.
Exchange 1
How should treatment decisions be weighted when patients require rapid symptom relief or have symptomatic or high-burden lesions?
Professor Hailiang Zhang
Huadong Hospital, Fudan University
Patients with high tumor burden who require rapid symptom relief often have highly aggressive disease that progresses quickly. In the CheckMate 214 trial, more patients in the dual immunotherapy arm experienced early disease progression than in the immunotherapy–TKI combination arm. One reason is that some patients have primary resistance to immunotherapy. These patients tend to have faster disease progression, more aggressive tumors, and greater tumor burden. Rapid progression can quickly become life-threatening.
For these patients, TKIs must be introduced early, making an immunotherapy–TKI combination a more appropriate choice. The targeted agent first suppresses angiogenesis and modifies the tumor immune microenvironment, after which the PD-1 inhibitor activates the immune system to attack tumor cells.
Although occasional cases of rapid tumor shrinkage—almost miraculous responses—are observed with immunotherapy monotherapy in patients with rapidly progressing disease, monotherapy is generally unable to control the disease in most cases. Immunotherapy–TKI combinations achieve faster tumor shrinkage and can provide rapid, comprehensive tumor control early in treatment.
Once the disease has been controlled initially, the patient’s overall condition may improve, allowing subsequent treatment strategies to be adjusted through a multidisciplinary approach. For selected lesions, local treatments such as stereotactic body radiotherapy (SBRT) can be added. If the patient’s physical condition permits, the systemic treatment regimen may even be switched to achieve better disease control.
The priority at the initial stage is to achieve rapid and comprehensive tumor control. Once explosive disease progression occurs, it can be extremely difficult to regain control.
Round Summary
Areas of Agreement
Both professors agreed that dual immunotherapy and immunotherapy–TKI combinations are currently guideline-recommended first-line options. Dual immunotherapy offers durable responses and long-term survival benefits in patients with intermediate- or poor-risk advanced clear cell renal cell carcinoma (ccRCC), whereas immunotherapy–TKI combinations provide faster tumor shrinkage and greater accessibility.
For patients with high tumor burden, rapid disease progression, or a need for rapid tumor shrinkage, greater weight should be given to immunotherapy–TKI combinations in treatment decisions. Dual immunotherapy requires particular vigilance for immune-related adverse events and close follow-up.
Areas of Disagreement
Professor Hailiang Zhang emphasized that dual immunotherapy may offer some patients the opportunity for long-term survival and even a potential cure, and advocated its active use in appropriately selected patients with ccRCC.
Professor Xuewen Jiang, drawing on the VEGF-enriched biology of RCC, the challenges of managing immune-related toxicities, and the accessibility of drugs and insurance coverage, argued that immunotherapy–TKI combinations should remain the mainstream first-line approach at present. Other approaches, such as bispecific or combination antibodies paired with TKIs, should be explored through clinical trials and individualized treatment strategies.
Expert Summary and Outlook
Professor Xuewen Jiang
Qilu Hospital of Shandong University
Thank you, Moderator. Today, Professor Hailiang Zhang and I had the opportunity to discuss first- and second-line treatment strategies and approaches. Current treatment paradigms are relatively mature and standardized, but decisions must still be individualized according to each patient’s specific circumstances.
The IMDC risk score primarily reflects performance status and hematologic parameters, but it does not account for sarcomatoid differentiation or the proportion of sarcomatoid components. Patients with sarcomatoid differentiation, in particular, tend to have highly aggressive disease and a high degree of malignancy. Certain molecular alterations are also associated with distinct disease characteristics. For example, patients with PBRM1 mutations may exhibit different patterns of tumor aggressiveness and progression.
For these special patient populations, we have been conducting multidisciplinary team (MDT) discussions since 2016–2017, following the approach of Professor Dingwei Ye’s team at Fudan University Shanghai Cancer Center. I strongly endorse this model.
I also agree with Professor Zhang’s point that local treatment should be incorporated in subsequent treatment lines once systemic therapy has achieved rapid tumor reduction. For example, stereotactic body radiotherapy (SBRT) can be added, and interventional embolization may be considered for selected lesions with abundant blood supply. Conversion therapy is another option for patients with metastatic renal cell carcinoma (mRCC): systemic therapy is first used to achieve good disease control, followed by resection of the primary tumor.
Through comprehensive treatment involving multiple disciplines and modalities, we should strive to prolong progression-free survival (PFS) and overall survival (OS) across first-line, second-line, and subsequent treatment lines in advanced RCC.
Campbell-Walsh Urology frequently notes that RCC is the most lethal malignancy among urologic cancers. Even after multiple lines of treatment, OS rarely exceeds 60–70 months. In contrast, patients with prostate cancer can still achieve relatively long overall survival after multiple treatment lines, while highly aggressive forms of bladder cancer account for a comparatively smaller proportion of cases.
For mRCC, regardless of whether targeted therapy combinations or other treatment approaches are selected, overall survival remains unsatisfactory. Moving forward, we need to rely more heavily on multidisciplinary care to develop individualized treatment plans for every patient. Decisions such as whether to administer systemic therapy or perform surgery first, and when to incorporate local treatment during the course of therapy, must be tailored to the individual.
Professor Hailiang Zhang
Huadong Hospital, Fudan University
I am very pleased to have participated in today’s program with Professor Xuewen Jiang.
First and foremost, treatment should be administered strictly in accordance with clinical guidelines and evidence-based medicine.
We are living in a remarkable era. In both renal cell carcinoma (RCC) and urothelial carcinoma, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) have improved dramatically compared with five to ten years ago. Median OS in RCC has now reached over 40 months, approaching 50 months, while in urothelial carcinoma it has exceeded 32 months—outcomes that would have been unimaginable in the past. Nearly half of patients with advanced RCC can now survive for five years, largely thanks to immunotherapy–TKI combination therapy.
Immunotherapy-based combination regimens are now available in both the first- and second-line settings. First-line immunotherapy–TKI combinations have primarily focused on intermediate- and poor-risk patients, but they are also effective in favorable-risk patients. Relevant studies have shown that these combinations provide a survival benefit over monotherapy. In other words, combining one targeted agent with one immunotherapy agent—“1 + 1”—achieves at least more than the effect of either agent alone.
In the second-line setting, new evidence has also emerged supporting immunotherapy–TKI combinations for patients whose disease has progressed on first-line TKI therapy.
However, the real challenge today is the lack of sufficient evidence to guide treatment selection after failure of first-line immunotherapy–TKI combinations or dual immunotherapy. Although regimens combining TKIs with HIF-2α inhibitors have emerged, the level of evidence remains insufficient, and drug accessibility and cost still prevent many patients from affording these treatments. There is still a long way to go, particularly in conducting more domestic research on novel agents.
In my view, first-line treatment has reached a plateau, and achieving further breakthroughs will be extremely difficult. In Merck’s Phase III LITESPARK-012 trial, the “luxury triplet” regimen combining a TKI, a PD-1 inhibitor, and a HIF-2α inhibitor failed to outperform the doublet of a PD-1 inhibitor plus a TKI in terms of the two co-primary endpoints, PFS and OS.
This suggests that dual immunotherapy–TKI combinations have already reached a relatively high efficacy–cost-effectiveness plateau. First-line treatment may remain at this level for the next decade unless a major breakthrough emerges in areas such as cellular therapy.
Therefore, the most important issue at present is how to improve the efficacy of second-line treatment after first-line failure, prolong second-line PFS, and ultimately improve OS. I hope that, under the leadership of experts across China, we can conduct more research and further extend the survival of Chinese patients with RCC.
Thank you.
This article was compiled from the recording of the “Getting to the Bottom of the Debate 2.0” academic debate and is intended for medical professionals only. The views expressed by the experts are their own academic opinions and do not constitute clinical treatment recommendations.
Professor Hailiang Zhang
Professor Xuewen Jiang
