Ceasing or pausing a combination of the immune checkpoint inhibitor nivolumab and the oral tyrosine kinase inhibitor (TKI) axitinib after 2 years may be safe among patients with metastatic renal cell carcinoma who achieved a positive response to this treatment, according to updated analysis of a multicenter, investigator-initiated, phase I/II study of axitinib with nivolumab. Zibelman et al presented their findings at the 2025 ASCO Genitourinary Cancers Symposium (Abstract 548).
Background
The combination of immune checkpoint inhibitors and TKIs is considered the standard of care in patients with renal cell carcinoma. In the 7 years since the initiation of this study, novel therapeutics have surpassed the performance of nivolumab plus axitinib—making the approval of the drug combination unlikely and unnecessary.
Previous studies exploring similar drug combinations have not assessed the potential of ceasing therapy, however.
Treatment can cause adverse effects such as diarrhea, stomatitis, fatigue, loss of appetite, and skin changes to the hands and feet. Oral TKIs can lead to cumulative toxicities because they are administered daily. These adverse effects generally disappear when the drugs are ceased.
Study Methods and Results
In the phase I/II clinical trial, researchers examined the outcomes of 26 patients with relapsed metastatic renal cell carcinoma treated with a combination of nivolumab plus axitinib in an initial dose finding phase I portion and a phase II portion including two parallel arms: patients with mRCC who were treatment naïve (n = 20) and a second arm of patients (n = 6) previously treated with TKIs or a combination of immunotherapeutic agents.
In this current analysis, researchers presented final results from the previously treated cohort in the phase II portion of the study. Among six patients who completed 2 years of treatment with nivolumab/axitinib, five chose to stop one or both drugs after 2 years. These five patients remained progression-free with no need for additional therapy, with a median progression-free interval of 23.2 months. Adverse event data was similar to published data for immunotherapy/TKI combinations.
“Being able to take periods of time off treatment without fear that your cancer is going to immediately progress can be meaningful for patients,” explained lead study author Matthew Zibelman, MD, Associate Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center.
In addition to potentially avoiding adverse effects, ceasing or pausing therapy can reduce the amount of time patients spend visiting the clinic as well as costs for the health-care system.
Conclusions
“My main takeaway from this is that there are subsets of patients [who] can have durable disease control with these drugs, and they may not need to stay on both therapies. Careful patient selection can allow some patients to have long periods of time off continuous therapy,” highlighted Dr. Zibelman. “For patients who are using an oral therapy and an immunotherapy, if they are having good disease control at a certain point in time, they may be able to stop one or both therapies. It doesn’t have to be just this combination. It would apply to any of the combinations out there,” he emphasized.
The researchers expect their findings to apply to similar drugs. They plan to further evaluate outcomes in patients with renal cell carcinoma receiving first-line therapy as well as potential biomarkers of response or resistance that could be used to select patients who may benefit from different drug combinations.
Disclosure: For full disclosures of the study authors, visit asco.org.
