Cabozantinib and Atezolizumab in Metastatic Castration-Resistant Prostate Cancer
Patients with metastatic castration-resistant prostate cancer with extrapelvic nodal or visceral metastasis who were treated with the combination of cabozantinib plus atezolizumab had significantly improved time to disease progression compared with those who were treated with hormonal therapy. This research was presented by Neeraj Agarwal, MD, FASCO, and colleagues at the 2024 ASCO Genitourinary Cancers Symposium (Abstract 18).
Neeraj Agarwal, MD, FASCO
About the CONTACT-02 Study
“Metastatic castration-resistant prostate cancer remains a fatal disease, and real-world evidence indicates that the median overall survival for patients with metastatic castration-resistant prostate cancer that has progressed despite treatment with a novel hormonal therapy is less than 2 years. Furthermore, patients with metastatic castration-resistant prostate cancer with visceral metastasis fare even more poorly, particularly those with liver metastases, with a median overall survival of less than 14 months. This patient population constituted nearly a quarter of the CONTACT-02 patient population and experienced a magnitude of benefit consistent with that seen in the overall study population,” said lead study author Dr. Agarwal, of the Huntsman Cancer Institute at the University of Utah.
In the CONTACT-02 study, 507 previously treated patients were randomly assigned to receive either a combination of cabozantinib (a tyrosine kinase inhibitor) plus atezolizumab (a PD-L1 inhibitor; n = 253), or hormonal therapy (n= 254). Patients had a median age of 71 years and a median baseline prostate-specific antigen (PSA) score of between 25 and 34 ng/mL; approximately four of five patients had bone metastases, three of four had enlarged lymph nodes; and about 40% of patients had cancer with visceral metastases.
The primary endpoints of the study were radiographic progression–free survival in the first 400 randomly assigned patients and overall survival in all randomly assigned patients. The secondary endpoint was overall response rate.
After a median follow-up of 14.3 months, there was a statistically significant improvement in progression-free survival, as evidenced by a 35% reduction in the risk of disease progression or death in patients treated with cabozantinib plus atezolizumab compared with those treated with hormonal therapy (median progression-free survival = 6.3 months vs 4.2 months, hazard ratio [HR] = 0.65, P = .0007).
In patients with liver metastasis, radiographic progression–free survival was 6 months in those treated with the combination therapy compared with 2.1 months in patients treated with hormonal therapy. In patients who received prior docetaxel treatment, radiographic progression–free survival was 8.8 months in those treated with the combination therapy compared with 4.1 months in patients treated with hormonal therapy.
After a follow-up of at least 6 months, the overall response rate was also higher in patients who received cabozantinib plus atezolizumab compared with those who received hormonal therapy (13.6% [23/169] vs 4.2% [7/165], respectively).
Grade 3 and 4 adverse events occurred in 48% of those treated with cabozantinib plus atezolizumab and 23% of those treated with hormonal therapy, and grade 5 adverse events occurred in 9% vs 12%, respectively. The most frequent treatment-related grade 3 and 4 adverse events were hypertension, occurring in 7%, followed by anemia in 6% (which was less than in the control), diarrhea in 4%, and fatigue in 4%.
The CONTACT-02 study remains ongoing to collect overall survival data. The researchers also plan to analyze patient-reported outcomes.
ASCO Expert Perspective
“Patients with metastatic castration-resistant prostate cancer have a very poor prognosis. The combination therapy of atezolizumab and cabozantinib offers a unique clinically synergistic mechanism of action. This potentially expands the arsenal of treatment options for patients. Most importantly and refreshingly, this combination was active in a subset of patients that are most difficult to treat. For example, patients having aggressive features like visceral metastases. I am excited about the initial results in CONTACT-02,” said Mark T. Fleming, MD, an ASCO Expert.
Disclosure: The study was funded by Exelixis, Inc. For full disclosures of the study authors, visit coi.asco.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.