The phase 3, multi-center, open-label, randomized CONTACT-02 trial, directed by Neeraj Agarwal of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, was designed to evaluate the safety and efficacy of cabozantinib, a tyrosine kinase inhibitor (TKI), combined with immune checkpoint inhibitor (ICI) atezolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic soft-tissue metastases that had progressed on prior treatment with one androgen receptor pathway inhibitor (ARPI).
Published in The Lancet Oncology*, results of final analyses show a 35% reduction in the risk of disease progression or death in patients who received the cabozantinib-atezolizumab combination compared to those who were assigned to receive a second ARPI.
“Metastatic castration-resistant prostate cancer that has progressed on treatment with an androgen receptor inhibitor associates with poor outcomes and an overall survival rate of less than two years. The prognosis is even worse for patients with extrapelvic soft-tissue metastases, especially among those patients with liver metastasis,” said Joan Carles, a Medical Oncologist at the Vall d’Hebron University Hospital and co-leader of the Vall d’Hebron Institute of Oncology’s Prostate Cancer Group.
Chemotherapy or a second ARPI may be considered as treatment options for these patients (especially in the United States), although the optimal sequence of therapies remains undefined. Other systemic therapies, while available, are only offered to a subset of patients.
“The development of safe and effective new treatments with novel mechanisms of action for patients with mCRPC following disease progression on an ARPI remains an unmet clinical need,” added Carles.
This study enrolled 507 patients at 184 sites across 24 countries, who were randomized 1:1 to receive cabozantinib plus atezolizumab or a second ARPI. After a median follow-up of 11·8 months, progression-free survival was 6.3 months in patients treated with the investigational combination compared to 4.2 months in the ARPI group.
While overall survival was not statistically different between the two groups, findings showed an increase in median overall survival of approximately five months in patients with liver metastases.
“To our knowledge, this phase 3 trial had the highest percentage of patients with visceral, and primarily liver, metastases of any contemporaneous trial and is the first to demonstrate improved progression-free survival with a TKI-ICI combination over a second ARPI in this population,” observed Joan Carles.
“Upon evaluation by the different regulatory authorities and healthcare reimbursement systems, data from this study support the cabozantinib-atezolizumab combination as a new treatment strategy for these patients. Considering the lack of differentiated and broadly available options beyond chemotherapy or agents that directly inhibit androgen receptor signalling, new therapeutic avenues are particularly important in this patient population,” he concluded.
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Reference
*Agarwal N, Azad AA, Carles J, Matsubara N, Oudard S, Saad F, Merseburger AS, Soares A, McGregor BA, Zurawski B, Tsiatas M, North S, Bondarenko I, Alfie M, Bournakis E, Antonuzzo L, Evilevitch L, Simmons A, Wang F, Ferraldeschi R, Nandoskar P, Pal SK. Cabozantinib plus atezolizumab in metastatic prostate cancer (CONTACT-02): final analyses from a phase 3, open-label, randomised trial. Lancet Oncol. 2025 Jul;26(7):860-876. doi: 10.1016/S1470-2045(25)00209-8. Epub 2025 Jun 13.
