ASCO Expert Perspective
“Patients with metastatic castration-resistant prostate cancer have a very poor prognosis. The combination therapy of atezolizumab and cabozantanib offers a unique clinically synergistic mechanism of action. This potentially expands the arsenal of treatment options for patients. Most importantly and refreshingly, this combo was active in 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, ASCO Expert.
Study at-a-Glance
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Focus |
Metastatic castration-resistant prostate cancer with extrapelvic nodal or visceral metastasis |
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Population |
507 patients with cancer that had progressed on novel hormonal therapy. |
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Main Takeaway |
Patients with metastatic castration-resistant prostate cancer previously treated with novel hormonal therapy who received cabozantinib plus atezolizumab had better radiographic progression-free survival compared to patients treated with a second round of novel hormonal therapy. |
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Significance |
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Reno, Nevada (UroToday.com) -- Patients with metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic nodal or visceral metastasis who were treated with the combination therapy of cabozantinib plus atezolizumab had significantly improved time to disease progression compared to those who were treated with hormonal therapy. This research will be presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, taking place January 25-27 in San Francisco, California.
About the 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 two 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 Neeraj Agarwal, MD, from the Huntsman Cancer Institute at the University of Utah.
In the CONTACT-02 study, 507 previously treated patients were randomized to receive either a combination of cabozantinib – a tyrosine kinase inhibitor – plus atezolizumab – a programmed cell death protein 1 (PD-L1) inhibitor (n=253) – or hormonal therapy (n= 254). Tyrosine kinase inhibitors are a type of targeted therapy that blocks tyrosine kinase enzymes to stop cancer cells from growing. PD-L1 inhibitors are a form of immunotherapy that targets PD-1, a protein that is found on the surface of T cells, in order to allow the immune system to better eliminate the disease.
Patients were a median age of 71 years and had a median baseline prostate specific antigen (PSA) score between 25 and 34 ng/mL; approximately 4 out of 5 patients had bone metastases and 3 out of 4 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 (rPFS) in the first 400 randomized patients and overall survival (OS) in all randomized patients. The secondary endpoint was overall response rate.
Key Findings
- After a median follow-up of 14.3 months, there was a statistically significant improvement in the PFS, as evidenced by a 35% reduction in the risk of progression or death in patients treated with cabozantinib plus atezolizumab compared to those treated with hormonal therapy (median PFS 6.3 months versus 4.2 months, HR:0.65, p value: 0.0007).
- In patients with liver metastasis, rPFS was 6 months in those treated with the combination therapy compared to 2.1 months in patients treated with hormonal therapy.
- In patients who received prior docetaxel treatment, rPFS was 8.8 in those treated with the combination therapy compared to 4.1 months in patients treated with hormonal therapy.
- After a follow-up of ≥6 months, the overall response rate was also higher in patients who received cabozantinib plus atezolizumab compared to 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, while grade 5 adverse events occurred in 9% vs 12%, respectively. The most frequent treatment-related grade 3-4 adverse events were hypertension, occurring in 7%, followed by anemia in 6% (which was less than control), diarrhea in 4%, and fatigue in 4%.
Next Steps
The CONTACT-02 study remains ongoing to collect overall survival data and the researchers also plan to analyze patient-reported outcomes.
The study was funded by Exelixis, Inc.
Source: American Society of Clinical Oncology, Inc. (ASCO®). (2024). Combination of Cabozantinib and Atezolizumab Offers Hope for Patients With Type of Advanced Prostate Cancer with Poor Prognosis [Press release]. https://old-prod.asco.org/about-asco/press-center/news-releases/combination-cabozantinib-and-atezolizumab-offers-hope-patients?cid=DM16129&bid=339799059.