As reported in The Lancet Oncology by Agarwal et al, the phase III CONTACT-02 trial examined the survival benefit of cabozantinib plus atezolizumab vs switch of androgen receptor pathway inhibitor (ARPI) in patients with castration-resistant prostate cancer with extrapelvic soft-tissue metastases who had progressed on a previous ARPI.
Study Details
In the open-label trial, 575 patients from sites in 24 countries (in Europe, North America, Asia-Pacific, and Latin America) were randomly assigned between August 2020 and June 2023 to receive cabozantinib at 40 mg once daily plus atezolizumab at 1,200 mg every 3 weeks (n = 289) or ARPI switch (n = 286) to abiraterone at 1,000 mg once daily plus prednisone at 5 mg twice daily or enzalutamide at 160 mg once daily. The dual primary endpoints of the trial were progression-free survival in the first 400 randomly assigned patients and overall survival in all randomly assigned patients.
Key Findings
After a median follow-up of 11.8 months (interquartile range [IQR] = 9.9–19.3 months) in the first 400 randomly assigned patients, median progression-free survival was 6.3 months (95% confidence interval [CI] = 6.2–8.8 months) in the cabozantinib plus atezolizumab group vs 4.2 months (95% CI = 3.7–5.7 months) in the ARPI switch group (hazard ratio [HR] = 0.65, 95% CI = 0.50–0.84, P = .0007).
Subsequent systemic therapy was received by 46% of the cabozantinib plus atezolizumab group and 52% of the ARPI switch group, most commonly a taxane in both groups (73% and 87%).
After a median follow-up of 23.1 months (IQR = 17.4–30.5 months), median overall survival was 14.8 months (95% CI = 13.4–16.7 months) in the cabozantinib plus atezolizumab group vs 15.0 months (95% CI = 13.0–18.5 months) in the ARPI switch group (HR = 0.89, 95% CI = 0.72–1.10, P = .30). In a preplanned analysis censoring for any systemic nonprotocol anticancer medications, median overall survival was 17.2 vs 18.7 months (HR = 0.82, 95% CI = 0.61–1.09).
Grade 3 to 4 adverse events occurred in 56% of the cabozantinib plus atezolizumab group vs 26% of the ARPI switch group; the most common were hypertension (8%) and anemia (8%) in the cabozantinib plus atezolizumab group and anemia (6%) in the ARPI switch group. Treatment-related serious events occurred in 16% (most commonly diarrhea, in 2%) vs 4% of patients (most commonly increased alanine aminotransferase, in 1%). Adverse events led to a discontinuation of treatment in 17% vs 15% of patients. No treatment-related deaths were reported.
The investigators concluded: “Cabozantinib plus atezolizumab, a novel drug combination that does not directly target androgen receptor signaling, could be a useful treatment option for patients with [metastatic castration-resistant prostate cancer] and soft-tissue metastases who have progressed on an ARPI.”
Neeraj Agarwal, MD, of the Division of Medical Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Exelixis in partnership with Ipsen, Takeda, and Roche. For full disclosures of all study authors, visit The Lancet Oncology.
