New Prostate Cancer Drug Combo Shows Promise
Regimen delays disease progression for high-risk patients
A combination of cabozantinib and atezolizumab has demonstrated a significant benefit in delaying disease progression for men with metastatic castration-resistant prostate cancer (mCRPC). Final results from the CONTACT-02 trial indicate this pairing may offer a crucial advantage for a challenging patient group.
Advancing Treatment for mCRPC
The phase 3 CONTACT-02 trial revealed that cabozantinib (Cabometyx) paired with atezolizumab (Tecentriq) provided a statistically significant improvement in progression-free survival (PFS) when compared to standard androgen receptor pathway inhibitors (ARPIs). This finding is particularly relevant for patients with mCRPC who also have measurable extrapelvic soft-tissue metastases.
While the combination did not extend overall survival (OS), the enhanced PFS suggests it can play a role in managing disease growth, offering more time without progression for these individuals.
Trial Insights and Patient Profile
The open-label, randomized CONTACT-02 study involved 989 men diagnosed with mCRPC. Participants had experienced disease progression after at least one prior ARPI treatment and possessed measurable extrapelvic metastases. Out of these, 575 were randomly assigned to receive either the cabozantinib/atezolizumab combination or a different ARPI.
Patients in the study were typically 71 years old, with the majority being White or Asian. Nearly half had visceral metastases, and a substantial number also had bone metastases. Many had previously received docetaxel or their last ARPI for mCRPC.
“Patients with mCRPC whose disease has progressed on ARPI have a poor prognosis, with relatively short overall survival.”
—Neeraj Agarwal, MD
Efficacy and Safety Findings
Following a median follow-up of nearly 12 months, the cabozantinib-atezolizumab group experienced a median PFS of 6.3 months, compared to 4.2 months for those on ARPIs. This translates to a 35% reduction in the risk of disease progression or death.
The combination therapy also showed a higher objective response rate (13% versus 6%) and a greater proportion of patients experiencing tumor shrinkage. Disease control rates favored the experimental arm (72% vs. 53%).
Regarding safety, the cabozantinib-atezolizumab combination led to more frequent treatment-related adverse events, with 40% of patients reporting grade 3/4 events. Hypertension and anemia were the most common high-grade toxicities in this group.
Contextualizing the Results
CONTACT-02 marks a significant advancement as the first phase 3 trial to demonstrate a PFS improvement with a combined tyrosine kinase inhibitor and immune checkpoint inhibitor approach in mCRPC. This contrasts with other trials, such as IMbassador250, where atezolizumab combined with enzalutamide did not yield similar overall benefits in an unselected patient population.
These findings, published in The Lancet Oncology, suggest that cabozantinib plus atezolizumab warrants further investigation as a viable treatment option for this specific patient subgroup.
Globally, prostate cancer is a significant public health concern. In 2022, it was the most common cancer diagnosis among men in the UK, with over 52,000 new cases reported (Statista, 2024).
