Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A...

Area of Science:

• Oncology
• Immunotherapy
• Renal Cell Carcinoma Research

Background:

• First-line treatment for metastatic renal cell carcinoma (mRCC) typically involves combinations of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1.
• Standard therapy is administered irrespective of patient prognostic classification.

Purpose of the Study:

• To assess the feasibility and safety of discontinuing VEGFR-TKI therapy while maintaining anti-PD1/PD-L1 treatment in mRCC patients who have shown a response to the initial combination therapy.
• To establish a potential new treatment strategy for mRCC management.

Main Methods:

• A single-arm, phase 2 clinical trial was conducted involving treatment-naïve mRCC patients with prior nephrectomy and no symptomatic/bulky disease or liver metastases.
• Patients received axitinib (a VEGFR-TKI) combined with avelumab (an anti-PD-L1 ICI). After 36 weeks, responders interrupted axitinib and continued avelumab maintenance until disease progression.
• The primary endpoint was the rate of disease progression-free survival at eight weeks post-axitinib interruption. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Main Results:

• Of 79 enrolled patients, 75 were evaluated for efficacy. Axitinib was withdrawn in 29 patients (38%), with 72% achieving the primary endpoint of no progression at eight weeks.
• The overall population achieved a median PFS of 24 months, with a median OS not reached. The objective response rate (ORR) was 76% (12% complete response, 64% partial response).
• In patients who discontinued axitinib, adverse events (AEs) of any grade occurred in 59%, with 3% experiencing grade 3 or 4 AEs. The study's limitation is the absence of a comparative arm.

Conclusions:

• The TIDE-A study indicates that withdrawing VEGFR-TKI therapy while continuing ICI maintenance is a feasible strategy for selected mRCC patients responding to first-line combination treatment.
• Interrupting axitinib and continuing avelumab maintenance demonstrated reduced side effects and warrants further investigation as a novel approach to potentially delay tumor progression in mRCC.