Lower Fracture Rates in Patients Treated with Radium-223, Abiraterone or Enzalutamide, When Given Concurrently with Bone Health Agents: A Real-World Analysis

Trieu, Janson; Chang, Mark; Rojas, Vanessa; Varada, Neilmegh; Cao, Yen; Anderson, M.; Vogelzang, Nicholas J.

doi:10.1016/j.clgc.2022.04.015

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…22,23 However, other studies and meta-analyses indicate that the combination of radium-223 and AR-targeted therapy is effective, and the risk of fracture can be reduced by concomitant use of BHAs such as denosumab or zoledronic acid. [24][25][26][27][28][29][30][31] The ongoing…”

Section: Discussionmentioning

confidence: 99%

“…The ERA‐223 study indicated increased risk of fracture when abiraterone acetate and radium‐223 were used together versus abiraterone alone, 21 resulting in regulatory restrictions on this combination 22,23 . However, other studies and meta‐analyses indicate that the combination of radium‐223 and AR‐targeted therapy is effective, and the risk of fracture can be reduced by concomitant use of BHAs such as denosumab or zoledronic acid 24–31 . The ongoing phase 3 PEACE III study (NCT02194842) will assess the efficacy and safety of radium‐223 combined with enzalutamide.…”

Section: Discussionmentioning

confidence: 99%

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Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

Higano,

Dizdarevic,

Logue

et al. 2024

Cancer

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BackgroundRadium‐223 and taxane chemotherapy each improve survival of patients with metastatic castration‐resistant prostate cancer (mCRPC). Whether the radium‐223–taxane sequence could extend survival without cumulative toxicity was explored.MethodsThe global, prospective, observational REASSURE study (NCT02141438) assessed real‐world safety and effectiveness of radium‐223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy‐naive at radium‐223 initiation and subsequently received taxane chemotherapy starting ≤90 days (“immediate”) or >90 days (“delayed”) after the last radium‐223 dose.ResultsFollowing radium‐223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received both. Seventy‐three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium‐223 dose to first taxane cycle was 3.6 months (range, 0.3–28.4). Median duration of first taxane was 3.7 months (range, 0–22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3 months from radium‐223 initiation and 11.8 months from start of taxane therapy.ConclusionsIn real‐world clinical practice settings, a heterogeneous population of patients who received sequential radium‐223–taxane therapy had a low incidence of hematologic events, with a median survival of 1 year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium‐223.Clinical Trial RegistrationClinicalTrials.gov identifier NCT02141438.Plain Language Summary Radium‐223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium‐223. Among the 182 men treated with radium‐223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2 years after starting radium‐223 and 1 year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium‐223 treatment without increasing the risk of side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

Higano,

Dizdarevic,

Logue

et al. 2024

Cancer

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“…The occurrence rate of common side effects such as high blood pressure, nausea and edema is low. Studies have also shown that compared with young patients, elderly patients have similar characteristics of tolerance to abiraterone, and there will not be too many differences in treatment effects [18] . Overall, abiraterone is relatively safe treatment and can play a role in many aspects such as maintaining the androgen synthesis pathway, mediating the androgen receptor, and affecting the tumor microenvironment.…”

Section: A Number Of Clinical Studies Have Confirmed Thatmentioning

confidence: 99%

Comparative Study on the Effect of Docetaxel and Abiraterone in the Treatment of Metastatic Castration Resistant Prostate Cancer

Ma,

Chen

2024

IJPS

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The study explored to evaluate and compare the effect of docetaxel and abiraterone in the treatment of metastatic castration resistant prostate cancer. 40 metastatic castration-resistant prostate cancer patients were retrospectively analysed and were divided into 2 groups, A and B each of 20 individuals (n=20). Group A was treated with docetaxel+prednisone tablets, and group B was treated with abiraterone+prednisone tablets. After the treatment, the treatment effects, progression-free survival, 1 y survival rate, tumor marker index levels, residual urine volume, maximum flow rate of urine, testosterone, and prostate-specific levels before and after treatment were compared between the two groups. Prostate specific antigen and androgen receptor splice variant-7 levels were compared to evaluate the safety of the two groups. The total effective rate in group B was 85 %, which was significantly higher than that in group A (p<0.05). The progression-free survival in group B was 13.2 mo, while in group A it was 10.2 mo (p<0.05). There was no significant difference in 1 y survival rate between the two groups (p>0.05). The levels of tumor markers in group B were lower than those in group A (p<0.05). The reduction of residual urine volume in group B was higher than that in group A (p<0.05), and maximum flow rate was greater in group A than in group B (p<0.05). The levels of testosterone, prostate specific antigen and androgen receptor splice variant-7 were lower in group B than those in group A (p<0.05). The adverse reaction rate of group B was 15 % lower than that of group A (35 %) (p<0.05). Abiraterone has a good clinical effect, can effectively improve the clinical symptoms of patients, with high drug safety, and is worthy of promotion.

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“…Likewise, in the ongoing phase 3 trial PEACE III (NCT02194842), where enzalutamide monotherapy is compared to a combination of radium-223 and enzalutamide, the risk of bone fractures was almost abolished by mandatory administration of BPAs [ 10 , 11 ]. Recent real-world data studies have also reported lower fracture rates in patients with mCRPC receiving radium-223 and abiraterone or enzalutamide when they were concurrently treated with BPAs [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model

Suominen

Knuuttila²,

Sjöholm³

et al. 2023

Cancers

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An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.

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Lower Fracture Rates in Patients Treated with Radium-223, Abiraterone or Enzalutamide, When Given Concurrently with Bone Health Agents: A Real-World Analysis

Cited by 6 publications

References 20 publications

Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

Comparative Study on the Effect of Docetaxel and Abiraterone in the Treatment of Metastatic Castration Resistant Prostate Cancer

Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model

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