Kidney cancer is among the top 10 most common cancers in men and women, with more than 80,000 new cases expected in the U.S. in 2026. Kidney cancers don’t respond well to traditional chemotherapy and instead are treated with immunotherapy and targeted therapies.
“The earlier the stage that people are diagnosed, the higher the likelihood of cure,” says University of Colorado Anschutz Cancer Center member Elaine Lam, MD, professor in the Division of Medical Oncology in the CU Anschutz School of Medicine. “If it's stage I, II, or III, where it's able to be removed surgically, then patients have a good chance of cure. When it's metastasized, the chance of cure goes way down.”
Compounding the problem, Lam says, is that there’s no screening test for kidney cancer.
“The general, very nonspecific screening that primary care providers do every year is a urinalysis, looking for blood in the urine,” Lam says. “But that's not 100 percent. Most people are diagnosed incidentally with kidney cancer when they get imaging for other reasons, and the scans show a mass in the kidney.”
Trials of new treatments
Beyond surgery, treatment for kidney cancer typically involves either targeted therapy or immunotherapy, depending on how advanced the cancer is and if it has spread to other sites in the body. The CU Anschutz Cancer Center is on the front lines of finding better ways to treat the disease, enrolling patients in clinical trials of new medications and new combinations with existing medications to hopefully achieve better, more durable responses and increased longevity.
“We were part of the LITESPARK-005 trial that led to the approval of a drug called belzutifan for patients with metastatic clear cell renal cell carcinoma, which is the most common type of kidney cancer,” Lam says. “Belzutifan was originally approved in 2021 for patients with von Hippel-Lindau disease, or VHL, which is a genetic syndrome that predisposes people to developing certain kinds of tumors, including kidney cancer, pancreatic tumors, brain tumors, and tumors in the eye. But even in patients who don't have VHL syndrome, the majority of clear cell kidney cancers have an acquired VHL mutation. The phase 3 LITESPARK-005 study in patients with metastatic clear cell kidney cancer found that belzutifan significantly improved progression-free survival and tumor response rates compared to standard everolimus. This study was practice-changing and introduced a new way to treat metastatic kidney cancers.”
Lam and colleagues also participated in the LITESPARK-011 study, an international study evaluating the combination of the immunotherapy drug pembrolizumab with belzutifan as adjuvant or preventative treatment in patients with non-metastatic kidney cancers who underwent surgery but were at high risk of recurrence. The results were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium on February 27.
The combination of belzutifan and pembrolizumab, compared to pembrolizumab alone, led to a 28% reduction in the risk of disease recurrence or death, making it the first adjuvant phase 3 trial in kidney cancer to show a significant benefit for a combination therapy versus an active immunotherapy comparator.
The CU Anschutz Cancer Center is currently enrolling patients to several important clinical trials for advanced kidney cancer. The Alliance STRIKE trial, a phase 3 nationwide study involving hundreds of academic and community cancer clinics, is evaluating the effectiveness of adding the blood-vessel-targeting drug tivozanib to pembrolizumab, the standard-of-care immunotherapy drug prescribed after surgery to keep the cancer at bay. Corbin Eule, MD, assistant professor in the Division of Medical Oncology, is the local principal investigator.
“Combinations of immunotherapy and blood-vessel targeting therapies are the mainstay of treatment for patients with metastatic renal cell carcinoma. This study evaluates this strategy in the adjuvant setting, to try to prevent recurrence or metastasis. While many patients with stage II and III kidney cancers are cured with surgery, some patients have a high risk of recurrence after surgery,” Lam says.
Another study is the phase 1 Hibercell study, which is looking at the effectiveness of combining a novel drug called HC-7366 with belzutifan or cabozantinib in patients with metastatic renal cell carcinoma. Lam is the local principal investigator.
“This is a phase I study in a later situation in the metastatic kidney cancer setting, when patients have progressed after standard immunotherapy and blood-vessel-targeting therapy,” Lam says. “We want to find out if that combination has synergy in the treatment of patients with metastatic kidney cancer after progressing on standard therapies.”
Reading the results
The LITESPARK-005 study led to the FDA approval of belzutifan for patients with advanced renal cell carcinoma in December 2023. Since then, Lam has seen many patients benefit from this new treatment option. She’s hopeful the current trials will help even more people.
“We've needed new, novel approaches to treating metastatic kidney cancer for a long time,” she says. “Up until very recently, we’ve only had immunotherapy or blood-vessel-targeting drugs. The work with newer strategies, newer mechanisms of action, is very exciting.”
Also exciting for Lam is to be part of the CU Anschutz Cancer Center, which is a National Cancer Institute-designated Comprehensive Cancer Center and part of the National Comprehensive Cancer Network, a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research, and education.
“We see a lot of patients from throughout Colorado and the surrounding states — Wyoming, Nebraska, New Mexico,” she says. “It’s great to have clinical trials like these to move the field forward and to bring additional options and hope for patients with kidney cancer.”
