A New Option for Advanced Renal Cell Carcinoma
- For patients with advanced kidney cancer whose disease progresses after immunotherapy, deciding what treatment comes next can be challenging. A newly approved combination of targeted treatments WELIREG (belzutifan) and LENVIMA (lenvatinib) offers another option.
- In the Phase 3 LITESPARK-011 trial, the combination helped patients with the most common subtype of advanced renal cell carcinoma, clear cell renal cell carcinoma, go longer without their cancer worsening and produced higher tumor response rates than cabozantinib, another option for advanced kidney cancer.
- However, a significant overall survival benefit was not established.
- Doctors emphasize that treatment decisions should be individualized, weighing the potential benefits of the combination against side effects such as anemia, low oxygen levels and heart problems.
The U.S. Food and Drug Administration (FDA) has approved WELIREG (belzutifan) plus LENVIMA (lenvatinib) for adults with the most common subtype of advanced renal cell carcinoma (RCC), clear cell renal cell carcinoma, who have previously received a PD-1 or PD-L1 inhibitor, a type of immunotherapy.
Read MoreThe combination is the first approved treatment pairing two specific targeted drugs, a HIF-2 alpha inhibitor and a multi-targeted VEGFR tyrosine kinase inhibitor, for this patient population.
“For patients and their doctors, it offers a defined path forward at a point in care where options have historically been limited,” Kogan says.
What Did the Trial Find?
The FDA’s decision was based on results from the Phase 3 LITESPARK-011 clinical trial, which enrolled 747 patients with advanced clear cell renal cell carcinoma whose cancer had progressed following immunotherapy.
Researchers compared WELIREG (belzutifan) plus LENVIMA (lenvatinib) with cabozantinib, an established treatment for advanced kidney cancer.
The results showed that patients receiving the new combination experienced:
- Longer progression-free survival: A median of 14.6 months before their cancer worsened or they died, compared with 10.6 months for patients receiving cabozantinib
- Higher response rates: Approximately 53% of patients receiving the combination saw their tumors shrink or disappear, compared with 40% receiving cabozantinib
- Reduced risk of progression or death: The combination lowered this risk by 26% compared with cabozantinib during the study
Final trial findings, presented at the 2026 European Society for Medical Oncology (ESMO) Congress, reinforced the benefits seen in earlier analyses. Patients receiving the combination also experienced longer-lasting responses, with a median duration of 22 months compared with 11.9 months for those receiving cabozantinib.
While these findings represent meaningful progress, the trial did not establish a statistically significant improvement in overall survival, or how long patients lived.
Kogan emphasizes that the results offer physicians important evidence when discussing treatment decisions with patients.
“First and foremost, I want them to have confidence that this new treatment option is supported by rigorous evidence,” she says.
Understanding Advanced Kidney Cancer
Renal cell carcinoma is the most common type of kidney cancer in adults. Clear cell renal cell carcinoma is its most common subtype.
When kidney cancer is advanced, it may have grown into surrounding tissues or spread to other parts of the body, such as the lungs, bones or liver.
Treatment often involves medications that work throughout the body, including immunotherapy and targeted therapies.
Immunotherapy helps the immune system recognize and attack cancer cells. PD-1 and PD-L1 inhibitors work by blocking signals that cancer cells can use to evade the immune system.
What Do Checkpoint Inhibitors Do for Cancer?
Although these treatments have significantly changed how advanced kidney cancer is managed, they do not work indefinitely for everyone.
When cancer progresses, doctors must consider additional treatment options based on the patient’s prior therapies, overall health and treatment goals.
How Does the Combination Work?
WELIREG (belzutifan) works by blocking a protein called HIF-2 alpha, which plays a role in the growth of certain kidney cancers. LENVIMA (lenvatinib) targets proteins involved in tumor growth and the formation of blood vessels that supply tumors.
Together, the medications attack cancer through different biological pathways.
Like other cancer treatments, the combination carries risks that patients should discuss with their care teams.
Common side effects include:
- Fatigue
- High blood pressure
- Diarrhea
- Nausea
- Anemia
Anemia occurs when the body doesn’t have enough healthy red blood cells to carry oxygen, potentially causing fatigue, weakness or shortness of breath. More serious complications can include low oxygen levels and heart problems.
In LITESPARK-011, serious adverse reactions occurred in 54% of patients receiving the combination. Physicians must weigh potential benefits against these risks when determining whether treatment is appropriate.
While the results offer another treatment option, doctors emphasize that the combination may not be appropriate for every patient.
“This is a good step moving forward to have another option for our patients, but I would choose this combo for selective patients, perhaps those who have bulky disease and who need a response more quickly, and patients would have to be told about the side effects of anemia,” Dr. Sandy Srinivas, a medical oncologist at Stanford Cancer Center, previously told SurvivorNet.
Expanding Treatment Options Throughout the Kidney Cancer Journey
The latest approval builds on years of research involving LENVIMA (lenvatinib), which Eisai developed and first launched in 2015.
The medication is now part of three FDA-approved combination regimens used at different points in the treatment of advanced kidney cancer.
These include LENVIMA (lenvatinib) with KEYTRUDA (pembrolizumab) as an initial treatment, LENVIMA with everolimus following prior anti-angiogenic therapy, and now LENVIMA with WELIREG (belzutifan) following PD-1 or PD-L1 immunotherapy.
For patients, having additional treatments available at different stages of the disease can make an important difference.
“Together, these regimens give patients treatment options across the course of their care, whether they are starting therapy or facing disease progression after a PD-1 or PD-L1 inhibitor,” Kogan explains.
She says the next priority is ensuring physicians, including those practicing in community settings, understand the clinical evidence and how the treatment may fit into patient care.
That includes sharing the full body of evidence from LITESPARK-011 through peer-reviewed research, presentations at major medical conferences and educational initiatives that help physicians apply the findings to patients in everyday clinical practice.
Beyond the clinical data, Kogan says the approval reflects the importance of listening to patients and families as new cancer treatments are developed. For people facing advanced kidney cancer, the approval offers another possibility at a difficult point in their treatment journey — and underscores the importance of continued research into therapies that may help patients live longer without their disease progressing.
Questions to Ask Your Doctor
If your kidney cancer has progressed after immunotherapy, consider asking your care team:
- Am I a candidate for WELIREG (belzutifan) plus LENVIMA (lenvatinib) based on my cancer type and previous treatments?
- How does this combination compare with other treatment options available to me?
- What do the clinical trial results mean for my chances of responding to treatment or delaying cancer progression?
- What side effects should I watch for and how would we manage them?
- How will we monitor whether the treatment is working, and what options would I have if my cancer progresses again?
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