Randomized phase II trial of neoadjuvant androgen deprivation therapy plus abiraterone and apalutamide for patients with high-risk localized prostate cancer: Pathologic response and PSMA imaging correlates

Autor: Diogo Assed Bastos, Rafael Coelho, Leonardo Cardili, Felipe Galiza, Eder Nisi Ilario, Públio Viana, Claudio Bovolenta Murta, Giuliano Guglielmetti, Mauricio Cordeiro, Jose Pontes Jr, David Queiroz Borges Muniz, Jamile Almeida Silva, Jose Mauricio Mota, Guilherme Fialho de Freitas, Katia Ramos Moreira Leite, Carlos Alberto Buchpiguel, William Carlos Nahas
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:5085-5085
ISSN: 1527-7755
0732-183X
Popis: 5085 Background: Patients (pts) with high-risk localized prostate cancer (HRLPC) have a significant risk of disease recurrence and metastasis after radical prostatectomy (RP). Neoadjuvant therapy remains investigational but there may be a role for the next-generation androgen signaling inhibitors. We sought to evaluate pathologic and imaging response after the intense neoadjuvant approach. Methods: This is a phase II investigator-initiated randomized trial of 3-month neoadjuvant therapy with goserelin (androgen deprivation therapy, ADT) + abiraterone acetate and prednisone (AAP arm) or AAP + apalutamide (A-APA arm) before RP for pts with HRLPC (Gleason ≥ 8 and/or cT3N0-1 and/or PSA ≥ 20 ng/mL). The primary endpoint was the rate of pathologic complete response (pCR) or minimal residual disease (MRD, tumor ≤ 0.5 cm). The secondary endpoints were safety, rate of residual cancer burden ≤0.25 cm3 (RCB = tumor volume x cellularity), Gallium 68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance correlates and rate of biochemical relapse (BR). Results: Sixty-two pts were randomized to A-APA (N = 31) or AAP (N = 31). Median age was 65 (range 47-77) years. NCCN risk groups included high-risk disease in 19%, very high-risk in 76% and regional (N1) disease in 5% (79% cT3, 65% Gleason 8-10, 57% PSA ≥ 20 ng/mL). Outcomes after intense neoadjuvant ADT are described in the Table. There was no statistically significant difference between study arms regarding pCR/MRD or RCB ≤ 0.25 cm3 rates. Patients with complete PSMA-PET response (psmaCR) demonstrated a RCB ≤ 0.25 cm3 rate of 50% compared to 7.5% in pts without a psmaCR ( P= 0.001). The rate of BR was 14% for pts with RCB ≤ 0.25 cm3 versus 38% in pts with RCB > 0.25 cm3 ( P= 0.118). At current median follow-up of 2.6 years, all patients with both psmaCR and RCB ≤ 0.25cm3 (N = 11, 18%) are free of BR. There were 2 grade (G) 5 adverse events (AEs) in the AAP arm (pulmonary embolism and sudden death, both after surgery). Nine (14.5%) pts (6 in A-APA; 3 in AAP) experienced G3-4 treatment-related AEs. The most common G3-4 AEs were hypertension (11.3%), AST/ALT elevations (3.2%) and skin rash (1.6%). Conclusions: No difference in pCR or MRD was observed between arms. Although pCR or MRD after intense neoadjuvant ADT was infrequent, a significant proportion of pts achieved a favorable pathologic response with RCB ≤ 0.25 cm3. PSMA-PET response is a potential surrogate for pathologic response. Clinical trial information: NCT02789878. [Table: see text]
Databáze: OpenAIRE
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