CONTACT-2 Shows Benefit of Cabozantinib Combination for mCRPC

Cabozantinib plus atezolizumab significantly improves radiographic progression-free survival (rPFS) versus second novel hormonal therapy (NHT) in patients who had progressed on a prior NHT and have metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic nodal or visceral disease, according to results of the CONTACT-2 study presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Patients who have progressed on a prior NHT and have mCRPC with extrapelvic nodal or visceral metastasis generally have a poor prognosis and limited treatment options outside of chemotherapy.

Neeraj Agarwal, MD, FASCO, and colleagues designed CONTACT-2 to randomize (1:1) patients with mCRPC with disease progression on 1 prior NHT to receive cabozantinib plus atezolizumab (n=253) or abiraterone plus prednisone or enzalutamide (control; n=254). Patients were stratified by liver metastasis, prior docetaxel for metastatic castration-sensitive prostate cancer (mCSPC), and prior NHT for mCSPC/M0CRPC/mCRPC.

Key eligibility criteria included measurable extrapelvic nodal or visceral disease, Eastern Cooperative Oncology Group performance status ≤1, and ongoing androgen deprivation therapy. Docetaxel was allowed for mCSPC.

Dual primary end points were rPFS in the first 400 randomized patients (PITT) and overall survival (OS) in all randomized patients (ITT).

At the data cutoff (February 28, 2023), Dr. Agarwal and colleagues noted that baseline and clinical characteristics were balanced between the investigative and control arms: 25% and 26% had liver metastasis, 21% and 20% received docetaxel for mCSPC, and 72% and 74% received first NHT for mCRPC, respectively. The median follow-up was 12.0 months for the ITT population and 14.3 months for PITT.

Results showed that the median rPFS was significantly longer for patients receiving cabozantinib plus atezolizumab compared with those receiving control (6.3 months vs 4.2 months, respectively; hazard ratio [HR], 0.65; 95% CI, 0.50-0.84; P=.0007), including in subgroups with liver metastasis (6.0 vs 2.1 months, respectively; HR, 0.47; 95% CI, 0.30-0.74) or prior docetaxel treatment for mCSPC (8.8 vs 4.1 months, respectively; HR, 0.55; 95% CI, 0.32-0.96).

Objective response rate, a secondary end point of the study, was higher in the investigative arm versus the control arm, with follow-up of at least 6 months in ITT (13.6% vs 4.2%, respectively). Median duration of response was 9.7 months versus not reached, respectively, and time to response was 2.3 months versus 4.6 months.

Researchers acknowledged that treatment-emergent adverse events (TEAEs) occurred in 97% versus 87% of patients, respectively, with grade 3/4 events of 48% versus 23%. Grade 5 TEAEs occurred in 9% versus 12% of patients, and no grade 5 treatment-related AEs occurred in either arm. TEAEs led to the discontinuation of all treatment components in 16% and 15% of patients, respectively.

“CONTACT-02 is the only phase 3 study of an [immune checkpoint inhibitor]-based regimen to show a significant and clinically meaningful improvement in rPFS in prostate cancer with visceral metastasis,” study authors concluded, adding that follow-up for OS is ongoing.