A new analysis suggests that patients with metastatic renal cell carcinoma (mRCC) who achieve positive responses to combination therapy with nivolumab and axitinib may safely discontinue treatment after two years. These findings, presented at the 2025 ASCO Genitourinary Cancers Symposium, offer promising implications for treatment optimization in responsive patients.
Long-term Outcomes in Previously Treated Patients
The multicenter, investigator-initiated phase I/II study focused on patients with relapsed mRCC treated with the immune checkpoint inhibitor nivolumab plus the tyrosine kinase inhibitor (TKI) axitinib. In the cohort of previously treated patients, five out of six participants maintained progression-free status without requiring additional therapy, achieving a median progression-free interval of 23.2 months.
"Being able to take periods of time off treatment without fear that your cancer is going to immediately progress can be meaningful for patients," stated lead study author Matthew Zibelman, MD, Associate Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center.
Safety Profile and Treatment Burden
The combination therapy's adverse event profile aligned with previously published data for immunotherapy/TKI combinations. Common side effects typically include diarrhea, stomatitis, fatigue, loss of appetite, and skin changes to the hands and feet. Notably, these adverse effects generally resolve upon treatment discontinuation.
The study's findings suggest multiple benefits of treatment cessation, including:
- Reduction in cumulative toxicities from daily oral TKI administration
- Decreased frequency of clinic visits
- Lower overall healthcare system costs
Clinical Implications and Future Directions
"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," Dr. Zibelman emphasized.
The researchers anticipate these findings may extend beyond the specific nivolumab-axitinib combination to other immunotherapy-TKI combinations in the treatment landscape. Future research will focus on:
- Evaluating outcomes in first-line therapy patients
- Identifying potential biomarkers of response or resistance
- Developing criteria for patient selection for treatment discontinuation
While newer therapeutic combinations have surpassed nivolumab plus axitinib in recent years, these results provide valuable insights into optimizing treatment duration for patients receiving immunotherapy-TKI combinations for mRCC.
