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. (September 2022)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of cancer. Volume 173(2022)
• Page Start: 317
• Page End: 326
• Publication Date: 2022-09
• Subjects: Radium-223 -- AR-V7 -- Bone metastases -- Metastatic castration-resistant prostate cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.06.057
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Purpose: The paper aims to evaluate the efficacy and safety of 223 Ra in patients who progressed after first-line androgen deprivation therapy. Patients and methods: 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 223 Ra (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. Results: 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). 223 Ra was well tolerated; anaemia and thrombocytopenia were the most common grade 3/4 adverse events (5.8% and 11.5%, respectively). Conclusions: 223 Ra 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. Highlights: 223 Ra had a promising antitumour activity in patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases. 223 Ra 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.