Radium-223 for patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases progressing on first-line abiraterone acetate or enzalutamide: A single-arm phase II trial

• Published in: European journal of cancer (1990) Vol. 173; pp. 317 - 326
• Main Authors: Carles, Joan, Alonso-Gordoa, Teresa, Mellado, Begoña, Méndez-Vidal, María J., Vázquez, Sergio, González-del-Alba, Aránzazu, Piulats, Josep M., Borrega, Pablo, Gallardo, Enrique, Morales-Barrera, Rafael, Paredes, Pilar, Reig, Oscar, Garcías de España, Carmen, Collado, Ricardo, Bonfill, Teresa, Suárez, Cristina, Sampayo-Cordero, Miguel, Malfettone, Andrea, Garde, Javier
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2022; Elsevier Science Ltd
• Subjects: Abiraterone Acetate - therapeutic use; Acetic acid; Alternative splicing; Androgen Antagonists - therapeutic use; Androgen receptors; Androgens; Anemia; AR-V7; Asymptomatic; Benzamides; Body weight; Bone cancer; Bone metastases; Bone Neoplasms - secondary; Castration; Deprivation; Humans; Male; Metastases; Metastasis; Metastatic castration-resistant prostate cancer; Nitriles - therapeutic use; Phenylthiohydantoin; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - pathology; Radium; Radium-223; Receptors, Androgen; Safety; Survival; Thrombocytopenia; Tumors; AR-V7; Metastatic castration-resistant prostate cancer; Radium-223; Bone metastases
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.06.057

The paper aims to evaluate the efficacy and safety of 223Ra in patients who progressed after first-line androgen deprivation therapy. EXCAAPE (NCT03002220) was a multicentre, single-arm, open-label, non-controlled phase IIa trial in 52 patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases who have progressed on abiraterone acetate or enzalutamide, up to six doses of 223Ra (55 kBq/kg of body weight per month). The primary end-point was radiographic progression-free survival (rPFS). Secondary end-points included rPFS based on androgen receptor splice variant 7 (AR-V7) expression in circulating tumour cells (CTCs), overall survival, and safety. Median rPFS was 5.5 months (95% CI 5.3–5.5). Median rPFS of patients with AR-V7(−) CTCs was longer than that of patients with AR-V7(+) CTCs (5.5 versus 2.2 months, respectively; P = 0.056). Median overall survival was 14.8 months (95% CI 11.2–not reached) and was significantly greater for AR-V7(−) patients than for AR-V7(+) patients (14.8 months versus 3.5 months, respectively; P < 0.01). 223Ra was well tolerated; anaemia and thrombocytopenia were the most common grade 3/4 adverse events (5.8% and 11.5%, respectively). 223Ra seems to be a reasonable treatment for patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases progressing on novel hormonal therapy and had an acceptable safety profile. •223Ra had a promising antitumour activity in patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases.•223Ra showed an acceptable safety profile similar to that reported in other studies.•Overall survival of androgen receptor splice variant 7 (−) patients was significantly higher than androgen receptor splice variant 7 (+) patients.