Combination treatment with nivolumab plus axitinib has achieved a high response rate in treatment-naïve patients with metastatic renal cell carcinoma (RCC), results from a phase I/II trial show.


Combination systemic therapy with tyrosine kinase inhibitors (TKIs) and an immune checkpoint inhibitor are an established standard of care for patients with metastatic RCC. Several trials with different combinations of immune checkpoint inhibitors and TKIs are currently ongoing. Dr. Matthew Zibelman (Fox Chase Cancer Center) presented first results of a phase I/II study (NCT03172754) investigating the safety and efficacy of the TKI axitinib combined with the immune checkpoint inhibitor nivolumab.1

Patients & Processes

The trial was initiated before the results from various phase III studies of immune checkpoint inhibitor-TKI combinations were known. In the phase I part, the recommended dose for axitinib was established at 5 mg twice daily. The phase II part of the trial included two parallel arms: treatment-naïve mRCC patients and previously treated mRCC patients.

The primary endpoint of the study is objective response rate, and secondary endpoints are progression-free survival (PFS), overall survival (OS), and safety. Dr. Zibelman presented results from the treatment-naïve arm only. In this arm, 44 patients were enrolled. One withdrew consent but was included in the safety analysis, while 42 patients were evaluable for efficacy. The median age was 65 years.

Comparable Efficacy

Using the IMDC risk group grading, 18 patients (41.9%) were favorable risk, 22 patients (51.2%) were intermediate risk, and 3 patients (7 %) were poor risk. Median follow-up was 11.5 months. Objective response rate was 59.5%, with 2.4% complete responders and 57.1% partial responders. The disease control rate was 97.6%. Median PFS was 16.4 months, and median OS was not reached. OS was 87.1% at 12 months and 69.4% at 24 months. Adverse event data were similar to published data for immune checkpoint inhibitor/TKI combinations, with no grade 4-5 adverse events.

Discontinuation of axitinib for adverse events occurred in nine (20.5%) patients, with discontinuation of nivolumab in eight (18.2%) patients. Based on these results, Dr. Zibelman concluded that “the combination of axitinib plus nivolumab for treatment-naïve patients with metastatic RCC demonstrated efficacy comparable to available immune checkpoint inhibitor-TKI combinations with a similar safety profile.” He admitted that it was unlikely to move to a phase III trial given the wealth of immune checkpoint inhibitor-TKI combinations already available in this setting.


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