TKIs Take Lead After Immunotherapy in Metastatic Kidney Cancer

A real-world study presented at the 2025 International Kidney Cancer Symposium showed that adults with metastatic renal cell carcinoma who previously received one immune checkpoint inhibitor were most often managed with tyrosine kinase inhibitor (TKI)-based regimens in later treatment lines. These findings indicate that TKIs remained the predominant approach across the sequencing patterns evaluated, according to research.

The analysis examined treatment patterns in community oncology settings and focused on patients who later received two TKI-based regimens. Investigators found that, even following prior immunotherapy exposure, TKI-directed strategies continued to guide real-world care for this population.

Moreover, the investigators also showed how treatment sequencing varied across first, second, and later lines of therapy, offering insight into how clinicians navigate regimens once patients progress beyond immune checkpoint inhibitor-based treatment. This type of real-world information is particularly important for patients, since treatment choices made after immune checkpoint inhibitor exposure often determine both disease control and quality of life.

“This evidence highlights the need for novel anticancer agents with distinct mechanisms of action and more favorable toxicity profiles to optimize outcomes for patients with metastatic renal cell carcinoma,” the study authors wrote in the poster.

Treatment Sequences in Metastatic Renal Cell Carcinoma After Immunotherapy

The study followed 293 adults treated between January 1, 2018, and March 31, 2023, with care documented through the iKnowMed electronic health record system used in U.S. Oncology Network and non-network clinics. All patients had received one immune checkpoint inhibitor regimen prior to starting the treatment sequences being evaluated. The group had a median age of 66 years and was predominantly male (74%). Most were White (326 patients, 89.5%), with a smaller proportion of Black patients (38 patients, 10.5%). A majority had clear-cell disease, although a meaningful subset had non–clear-cell cancers.

At the start of their post-immunotherapy treatment, most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 (56.0%), indicating they were somewhat limited in strenuous activity but still ambulatory. Risk levels based on the International Metastatic Renal Cell Carcinoma Database Consortium criteria showed that nearly half of patients fell into the intermediate-risk category (47.3%), while more than a third (36.9%) were considered poor risk.

To understand how treatment choices were made in practice, the investigators assigned each therapy to a specific line of treatment based strictly on the order in which therapies began and ended. The first treatment a patient received after completing their immune checkpoint inhibitor regimen was designated as the index treatment. From there, subsequent therapies were ordered according to the timing of their start and stop dates.

The study also evaluated clinical outcomes common to real-world oncology research. Real-world time on treatment was measured from the start of therapy until treatment was discontinued or the patient died. Real-world time to next treatment reflected the time between the start of a therapy and the initiation of the next one, discontinuation, or death. Overall survival was measured from the start date of the index therapy until the date of death, or the most recent visit recorded in the database.

Among the patients evaluated, TKI monotherapy emerged as the most common index treatment, being used in just over 42% of the cohort. Combination regimens that paired a TKI with an mTOR inhibitor were the next most frequent choice (20%), followed by mechanistic target of rapamycin (mTOR) inhibitor monotherapy (10%). A smaller number of patients received a combination of an immune checkpoint inhibitor and a TKI, although this was less common given that all patients in the study had already completed one immunotherapy regimen before entering the analysis.

Treatments prior to the index therapy commonly involved immunotherapy followed by a TKI, underscoring a common real-world pattern in which clinicians transition from immune-based therapy to targeted therapy as disease progresses.

The specific medicines used within these categories also reflected real-world practice patterns. Cabometyx (cabozantinib) and Inlyta (axitinib) were among the most frequently used TKIs, both as single agents and in combination regimens. Some patients received combinations such as Cabometyx with Keytruda (pembrolizumab) or everolimus with Lenvima (lenvatinib), illustrating the range of strategies clinicians employ when navigating later lines of therapy. As patients progressed through the second and third treatment lines, TKI-based approaches remained central. Even when combinations or alternative targeted therapies were used, TKIs continued to appear throughout the treatment sequence.

Key Takeaways for Patients Navigating Metastatic Kidney Cancer Treatment Choices

For individuals navigating metastatic renal cell carcinoma, especially after immunotherapy, treatment decisions can become complicated. This analysis confirms that TKI-based therapies continue to play a major role across treatment lines, even for patients who have already received an immune checkpoint inhibitor regimen. Although these therapies remain a mainstay, the study emphasized an unmet need for new treatment options that may offer improved safety and different mechanisms of action.

The research also provides patients with a clearer understanding of how care is being delivered in real-world settings, which can help support more informed conversations with oncology teams.

References

1. “Real-world Study of Treatment Patterns in Metastatic Renal Cell Carcinoma with Receipt of One Immune Checkpoint Inhibitor and Two TKIs,” by Dr. Neil J. Shah, et al. Presented at: 2025 International Kidney Cancer Symposium ; Nov. 13-15, 2025; Denver, Colorado. Abstract F5.

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