Cabozantinib Plus Atezolizumab Demonstrates Promise Among Patients With Metastatic Castration-Resistant Prostate Cancer and Soft-Tissue Metastases

According to results from the ongoing, phase 3 CONTACT-02 trial, cabozantinib plus atezolizumab demonstrated promise among patients with metastatic castration-resistant prostate cancer (mCRPC) and soft-tissue metastases who experienced disease progression after treatment with an androgen receptor pathway inhibitor (ARPI). 

In this open-label study, 575 patients were randomized on a 1-to-1 basis to receive either 40 mg of cabozantinib plus 1200 mg of atezolizumab (n = 289) or undergo ARPI switch to either 1000 mg of abiraterone plus 5 mg of prednisone or 160 mg of enzalutamide (n = 286). Patients were stratified based on presence of liver metastases, previous administration of docetaxel, and disease status at first ARPI administration. Primary end points included progression-free survival (PFS) and overall survival (OS). A key secondary end point was safety. 

At analysis, median PFS was 6.3 months in the cabozantinib plus atezolizumab arm and 4.2 months in the ARPI switch arm (hazard ratio [HR] 0.65; 95% confidence interval [CI], 0.50 to 0.84; P = .0007). Median OS was 14.8 months in the cabozantinib plus atezolizumab arm and 15 months in the ARPI switch arm (HR 0.89; 95% CI, 0.72 to 1.10; P = .30). Any-cause grade 3/4 adverse events occurred in 56% of patients and 26% of patients, respectively, and most frequently included hypertension and anemia. Serious treatment-related adverse events occurred in 16% of patients and 4% of patients, respectively, and most frequently included diarrhea (2%) in the cabozantinib plus atezolizumab arm and alanine aminotransferase increase in the ARPI switch arm (1%). Adverse events led to treatment discontinuation in 17% of patients and 15% of patients, respectively. No treatment-related deaths occurred.

“Cabozantinib plus atezolizumab, a novel drug combination that does not directly target androgen receptor signaling, could be a useful treatment option for patients with mCRPC and soft-tissue metastases who have progressed on an ARPI,” concluded Dr Agarwal et al. 

Source: 

Agarwal N, Azad AA, Carles J, et al. Cabozantinib plus atezolizumab in metastatic prostate cancer (CONTACT-02): final analyses from a phase 3, open-label, randomised trial. Lancet Oncol. Published online: June 13, 2025. doi: 10.1016/S1470-2045(25)00209-8