Conceptual image for prostate cancer treatment: © Dr_Microbe – stock.adobe.com
Cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) demonstrated a statistically significant improvement in progression-free survival (PFS) compared with androgen receptor pathway inhibitors (ARPIs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable extrapelvic soft-tissue metastases, according to final results from the phase 3 CONTACT-02 trial (NCT04446117). Although the regimen did not show an overall survival (OS) benefit, the PFS advantage suggests a potential role in delaying disease progression for this high-risk population.
Trial Design and Patient Population
CONTACT-02 was an open-label, randomized study that enrolled 989 men with mCRPC who had progressed on at least 1 prior ARPI and had measurable extrapelvic metastases. Eligible patients (n=575) were randomly assigned 1:1 to receive either cabozantinib (40 mg daily) plus atezolizumab (1200 mg every 3 weeks) or an alternative ARPI (abiraterone/prednisone for prior enzalutamide users or enzalutamide for prior abiraterone users). Stratification factors included liver metastases, prior docetaxel use, and disease status at first ARPI progression.
Baseline characteristics were well-balanced between arms. The median age was 71 years (range 66-75), with predominantly White (77%) or Asian (14%) patients. Nearly half (48%) had visceral metastases, including 23% with liver involvement, while 78% had bone metastases. Prior treatment exposure included docetaxel in 22% of patients in the metastatic hormone-sensitive setting, and 74% had received their last ARPI for mCRPC, with a median treatment duration of 12.0 months.
“Patients with mCRPC whose disease has progressed on ARPI have a poor prognosis, with relatively short overall survival,” wrote Neeraj Agarwal, MD, and colleagues.
Efficacy Outcomes
After a median follow-up of 11.8 months, the cabozantinib-atezolizumab group achieved a median PFS of 6.3 months (95% CI, 6.2–8.8) vs 4.2 months (95% CI, 3.7–5.7) in the ARPI arm (HR, 0.65; 95% CI, 0.50–0.84; P =.0007). The objective response rate (ORR) was higher with the experimental combination (13% vs 6%), and more patients experienced tumor shrinkage (68% vs 37%). Disease control rates favored cabozantinib/atezolizumab (72% vs. 53%), with fewer patients exhibiting progressive disease as their best response (17% vs 31%).
However, the final OS analysis showed no significant difference between arms (median OS 14.8 months vs 15.0 months; HR, 0.89; 95% CI, 0.72–1.10; P =.30).
Safety Profile
Treatment-related adverse events (TRAEs) were more frequent with cabozantinib-atezolizumab, with 40% of patients experiencing grade 3/4 events compared to 8% in the ARPI arm. The most common high-grade toxicities in the experimental arm were hypertension (8%) and anemia (8%), whereas anemia (6%) predominated in the control group. The median duration of treatment was 6.3 months (IQR, 3.4–11.0) for the combination versus 4.2 months (IQR, 2.1–9.0) for ARPIs. The safety profile was consistent with prior data for this combination.
CONTACT-02 represents the first phase 3 trial to show a PFS improvement with a tyrosine kinase inhibitor and immune checkpoint inhibitor combination in mCRPC. This contrasts with the negative IMbassador250 trial, where atezolizumab plus enzalutamide failed to improve outcomes in an unselected population, though a PFS benefit was observed in PD-L1–high subgroups.
The investigators concluded that cabozantinib plus atezolizumab warrants further exploration as a potential therapeutic option in this subpopulation.