CONTACT-02 Trial Results: Cabozantinib and Atezolizumab in Metastatic Prostate Cancer

The combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) reduced the risk of disease progression or death by approximately 35% in patients with metastatic castration-resistant prostate cancer (mCRPC) compared to a second androgen receptor pathway inhibitor (ARPI). According to results from the phase 3 CONTACT-02 trial published in The Lancet Oncology, this regimen offers a potential alternative for patients who have already progressed on initial hormonal therapies, though it did not demonstrate a statistically significant improvement in overall survival.

Clinical Efficacy and Progression Outcomes

The CONTACT-02 study enrolled over 500 men with mCRPC who had experienced disease progression after receiving an initial modern hormonal therapy, such as abiraterone or enzalutamide. Participants were randomized to receive either the combination of the tyrosine kinase inhibitor cabozantinib and the anti-PD-L1 antibody atezolizumab or a second ARPI.

After a median follow-up of 11.8 months, the study met its primary endpoint of progression-free survival (PFS). The median PFS was 6.3 months for the combination group compared to 4.2 months for those receiving a second ARPI. Despite this delay in tumor growth, the median overall survival (OS) was 14.8 months in the combination arm versus 15.0 months in the control group. Dr. Joan Carles, a medical oncologist at the Vall d’Hebron University Hospital in Barcelona, noted that mCRPC patients who progress after ARPI treatment typically face poor outcomes, with overall survival often falling below two years.

Safety Profile and Treatment Intensity

The therapeutic approach tested in CONTACT-02 is notably more intensive than standard hormonal treatments. Data from the trial indicate a higher incidence of severe adverse events among patients receiving the combination therapy. Specifically, grade 3-4 adverse events were reported in more than half of patients treated with cabozantinib and atezolizumab, compared to approximately a quarter of patients in the control group receiving a second ARPI.

The regimen is targeted at patients in good general health who have measurable extra-pelvic soft tissue metastases and have exhausted initial lines of treatment. While the study showed a potential survival benefit of approximately five months in a subgroup of patients with liver metastases, the lack of an overall survival advantage across the broader study population remains a key clinical finding.

Availability and Regulatory Status

Following the final analysis of overall survival data, Ipsen—the pharmaceutical company holding the rights to cabozantinib—decided in September 2024 against filing for regulatory approval of this specific combination outside of the United States and Japan.

Consequently, the cabozantinib-atezolizumab regimen is not currently considered a standard-of-care treatment in France. Patients interested in this therapeutic option should consult with their oncologists to determine if their clinical profile aligns with the criteria used in the CONTACT-02 trial and to discuss other validated treatment pathways available in clinical practice or through institutional expert centers.

Summary of Trial Findings

• Primary Endpoint: Median progression-free survival improved from 4.2 months (control) to 6.3 months (combination).
• Overall Survival: No statistically significant difference was observed, with 15.0 months for the control arm and 14.8 months for the combination.
• Adverse Events: Grade 3-4 events occurred in over half of the combination group, compared to approximately a quarter of the control group.
• Current Status: No plans for regulatory submission in Europe; treatment is currently limited to clinical trials or expert-led discussions.