Consolidative therapy for PSMA-avid lesions after 3 cycles of apalutamide plus androgen deprivation in metastatic hormone-sensitive prostate cancer: A prospective phase 2 single-arm trial

Metastatic hormone-sensitive prostate cancer (mHSPC) with limited metastatic burden presents a therapeutic challenge, with residual PSMA-avid disease post-androgen receptor pathway inhibitor (ARPI) treatment poorly characterized in prospective studies.

The CHAMPION trial (NCT05717582) was a multicenter, single-arm, phase II study designed to evaluate the efficacy and safety of a response-adapted treatment strategy incorporating consolidative therapy (TCT) for PSMA-avid residual resistant clones following ARPI in newly diagnosed mHSPC patients with ≤ 10 conventional imaging (CI)-defined distant metastases from March 2023 to August 2024. PSMA PET/CT scans were performed at baseline and after three cycles of apalutamide plus castration. Patients with > 10 PSMA-positive distant metastases continued apalutamide therapy, while those with ≤ 10 metastases underwent radical prostatectomy or radiotherapy, with stereotactic body radiotherapy targeting all remaining PSMA-positive lesions, if present. The primary endpoint was the proportion of patients achieving an undetectable PSA level (≤ 0.2 ng/mL) after 6 cycles of apalutamide.

A total of 48 patients with a median baseline PSA level of 56.8 ng/mL were enrolled. Baseline CI revealed 1–3 distant metastases in 31 patients (64.6%) and 4–10 in 17 patients (35.4%). Baseline PSMA PET/CT showed 1–3 distant metastases in 17 patients (35.4%), 4–5 in 8 patients (16.7%), and > 5 in 23 patients (47.9%); the most common PSMA-positive sites were bone (47/48, 97.9%), regional lymph nodes (28/48, 58.3%), and distant lymph nodes (15/48, 31.3%). After 3-cycle of apalutamide, two patients with > 10 PSMA-positive metastases continued apalutamide, while the remaining 46 with ≤ 10 metastases received TCT. After six cycles, the overall undetectable PSA rate was 95.8% (46/48; 95% CI: 86.0%-98.8%), a 29.1% increase from the 66.7% (32/48) observed after three cycles. Only two patients (4.2%) experienced grade ≥ 3 rash. Post-treatment, distant lymph node metastases showed the highest response rate at 93.3% (140/150), followed by vertebral column and pelvis bone metastases at 78.5% (255/325), and other bone metastases at 50.0% (58/116), with significant differences between each metastatic site pair (p < 0.0001).

This novel treatment paradigm, integrating PSMA PET/CT-guided TCT for residual lesions with intensified systemic therapy, was associated with a high PSA response rate and manageable adverse event profile in newly diagnosed mHSPC patients with ≤ 10 distant metastases.

Trial registration: NCT05717582.

Registered: 8 February 2023.