Cabozantinib plus atezolizumab improves PFS in mCRPC after progression on ARPI

In the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic soft-tissue metastases that has progressed on an androgen receptor pathway inhibitor (ARPI), the combination of cabozantinib plus atezolizumab appears to prolong progression-free survival (PFS), according to data from the open-label phase 3 CONTACT-02 trial.

CONTACT-02 included 575 patients (77 percent White) with mCRPC and measurable extrapelvic soft-tissue metastases (lymph node or visceral), had an ECOG performance status score of 0 or 1, and had progressed on one previous ARPI.

The patients were randomly assigned to receive cabozantinib (40 mg orally once daily) plus atezolizumab (1,200 mg intravenously once every 3 weeks) (n=289) or to switch to a different ARPI (either abiraterone 1,000 mg orally once-daily plus prednisone 5 mg orally twice-daily or enzalutamide 160 mg orally once-daily) (n=286).

Dual primary endpoints were PFS (assessed in the first 400 randomly assigned patients—PFS intention-to treat [ITT] population) and overall survival (OS; assessed in all randomly assigned patients—ITT population). Safety was evaluated in all patients who received at least one dose of study treatment.

Over a median follow-up of 11.8 months, PFS significantly increased in the cabozantinib plus atezolizumab arm than in the ARPI switch arm (median, 6.3 vs 4.2 months; hazard ratio [HR], 0.65, 95 percent confidence interval [CI], 0.50–0.84; p=0.0007).

For OS, no significant difference was observed between the two treatment arms after a median follow-up of 23.1 months (median, 14.8 vs 15.0 months; HR, 0.89, 95 percent CI, 0.72–1.10; p=0.30).

Any-cause grade 3–4 adverse events (AEs) occurred in 56 percent of patients on cabozantinib plus atezolizumab and in 26 percent of those who underwent an ARPI switch. Hypertension and anaemia were the most common AEs in the cabozantinib plus atezolizumab arm (8 percent for both) and anaemia in the ARPI switch arm (6 percent).

Serious AEs deemed related to treatment occurred in 16 percent of patients in the cabozantinib plus atezolizumab group and in 4 percent in the ARPI switch group.

AEs of any cause led to treatment withdrawal 17 percent of patients in the cabozantinib plus atezolizumab group and in 15 percent in the ARPI switch group. No treatment-related deaths were reported.