Final OS for CONTACT-02 trial in mCRPC

The CONTACT-02 trial demonstrated that the combination of cabozantinib and atezolizumab significantly improved progression-free survival (PFS) compared with second-line novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed following prior NHT and presented with extra-pelvic nodal or visceral metastases. The improvement was particularly notable in patients with liver metastasis and those who had previously received docetaxel for metastatic castration-sensitive prostate cancer (mCSPC).

“Despite recent advancements, outcomes remain poor for patients with mCRPC whose disease progresses after NHT – particularly for those with liver metastases,” stated Prof. Neeraj Agarwal (Huntsman Cancer Institute; University of Utah, UT, USA) [1].

CONTACT-02 (NCT04446117) is a global, randomised, phase 3 study that enrolled 575 patients with mCRPC who had progressed on 1 prior NHT and had measurable extra-pelvic soft tissue metastasis. Participants were randomised 1:1 to receive either cabozantinib and atezolizumab or a second-line NHT (i.e. abiraterone with prednisone or enzalutamide). The primary endpoints were PFS and overall survival (OS), with objective response rate (ORR) being a secondary endpoint.

After a median follow-up of 24.0 months, PFS was significantly improved in the cabozantinib and atezolizumab group (HR 0.65; 95% CI 0.50–0.84; P=0.0007). The final OS analysis did not reach statistical significance with a hazard ratio of 0.89 (95% CI 0.72–1.10; P=0.296). Notably, an improvement in OS was observed in subgroups with bone metastases (HR 0.79; 95% CI 0.63–1.00; P=0.046) and liver metastases (HR 0.68; 95% CI 0.47–1.00; P=0.051), populations in which disease is evolving away from androgen receptor signalling.

In terms of safety, the observed toxicities were manageable across both treatment arms. Grade 3–4 treatment-related adverse events (AEs) occurred in 40% of the participants in the cabozantinib and atezolizumab group and in 8% of those in the NHT group. The rates of treatment discontinuation due to AEs were similar between the 2 groups (5% vs 2%). Quality-of-life remained similar across both treatment arms.

Overall, while the OS results were not statistically significant, the PFS benefit coupled with an OS trend, particularly in patients with liver or bone metastasis, positions the combination of cabozantinib and atezolizumab as a potential therapeutic option in mCRPC patients with advanced disease. CONTACT-02 remains the only phase 3 study of an ICI-based regimen to show a significant and clinically meaningful improvement in PFS in patients with prostate cancer and visceral metastasis.

1. Agarwal N, et al. Cabozantinib (C) plus atezolizumab (A) versus 2nd novel hormonal therapy (NHT) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC): Final overall survival (OS) results of the phase III, randomized, CONTACT-02 study. Abstract LBA67, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024