According to results from the ongoing phase 3 CONTACT-2 trial, cabozantinib plus atezolizumab significantly improved radiographic progression-free survival (rPFS) compared to standard-of-care abiraterone plus prednisone or enzalutamide among patients with extrapelvic nodal or visceral metastatic castration-resistant prostate cancer (mCRPC) who experienced disease progression on neoadjuvant hormonal therapy. 

These results were presented by Neeraj Agarwal, MD, Huntsman Cancer Institute at the University of Utah, Salt Lake City, at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.

“[Patients] who have progressed on a prior [neoadjuvant hormonal therapy] and have mCRPC with extrapelvic nodal or visceral metastasis have a poor prognosis with limited, broadly available treatment options beyond chemotherapy,” stated Dr Agarwal and coauthors. “Cabozantinib promotes an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors.”

In this study, 507 patients with extrapelvic nodal or visceral mCRPC currently on androgen deprivation therapy who experienced disease progression on prior neoadjuvant hormonal, were randomized on a 1-to-1 basis to receive either 40 mg of cabozantinib plus 1200 mg of atezolizumab 4 times daily (n = 253) or abiraterone plus prednisone or enzalutamide. Randomization was stratified based on the presence of liver metastasis, prior docetaxel administration, and prior neoadjuvant hormonal therapy. Dual primary end points included rPFS assessed by blinded independent radiology committee per RECIST 1.1 in the preliminary intention-to-treat population (PITT) and OS in the intention-to-treat (ITT) population. Secondary end points included overall response rate (ORR), duration of response (DOR), time to response, and disease control rate (DCR). 

At a median follow-up of 14.3 months in the PITT population and 12 months in the ITT population, median rPFS was 6.3 months in the cabozantinib plus atezolizumab arm and 4.2 months in the control arm (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.50 to 0.84; P = .0007). For patients with liver metastasis, median rPFS was 6 months in the cabozantinib plus atezolizumab arm and 2.1 months in the control arm. For patients previously treated with docetaxel, median rPFS was 8.8 months in the cabozantinib plus atezolizumab arm and 4.1 months in the control arm. At a follow-up of ≥6 months, ORR was 13% in the cabozantinib plus atezolizumab arm and 4.2% in the control arm. Median DOR was 9.7 months in the cabozantinib plus atezolizumab arm and not reached in the control arm. Time to response was 2.3 months in the cabozantinib plus atezolizumab arm and 4.6 months in the control arm. DCR was 72.8% and 54.5%, respectively. At analysis, OS data was immature.  

Treatment-emergent adverse events occurred in 97% of patients in the cabozantinib plus atezolizumab arm and 87% of patients in the control arm. Grade 5 treatment-emergent adverse events occurred in 9% of patients in the cabozantinib plus atezolizumab arm and 12% of patients in the control arm. Treatment-emergent adverse events leading to discontinuation occurred in 16% and 15% of patients, respectively. No treatment-related deaths occurred in either arm. 

Dr Agarwal and coauthors concluded, “CONTACT-02 is the only phase 3 study of an [immune-checkpoint inhibitor]-based regimen to show a significant and clinically meaningful improvement in rPFS in prostate cancer with visceral metastasis. Follow-up for OS is ongoing.”

Source:

Agarwal N, Azad A, Carles J, et al. CONTACT-2: Phase 3 study of cabozantinib (C) plus atezolizumab (A) vs second novel hormonal therapy (NHT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 25-27, 2024; San Francisco, California. Abstract 18