ASCO 2016: Real world skeletal related events (SREs) associated with oral treatments in patients with metastatic castration-resistant prostate cancer (mCRPC)

Bone metastasis occurs in a majority of patients with advanced prostate cancer and represents a clinically significant issue in the management of these patients. Patients with bone metastases are at increased risk for skeletal complications, including pathologic fracture, spinal cord compression, and radiation or surgery to the bone, collectively termed skeletal-related events (SREs).1 SREs are associated with not only substantial morbidity but also greater mortality, increased pain, decreased quality of life, and increased treatment costs.2-6

Results from a retrospective analysis of a national claims database were presented at the 2016 American Society of Clinical Oncology (ASCO) meeting, June 3-7, in Chicago, IL. The study investigators endeavored to understand if the use of either abirertore acetate (ABI) and prednisone or enzalutamide (ENZ) in the treatment of metastatic castration-resistant prostate cancer (mCRPC) impacted the onset of skeletal related events.  Abiraterone acetate (ABI) with prednisone and enzalutamide (ENZ) are oral treatments for patients with mCRPC.

The methodology included use of a national health claims database of patients initiated on ABI or ENZ (index date) from 09/01/2012 to 06/30/2015 with: ≥1 non-diagnostic claim with a prostate cancer diagnosis (ICD-9-CM 185.xx) from 6 months prior to through 30 days after index date; ≥6 month pre-index and ≥3 months post-index health plan enrollment (retaining patients who died). Cohorts (ABI or ENZ) were defined based on the first medication initiated. Follow-up SREs (spinal cord compression, radiation to bone, pathological fracture, bone surgery) were assessed for patients without baseline SREs.

Descriptive analyses, Kaplan-Meier curves with log-rank tests, and Cox proportional hazards were used to compare ABI to ENZ cohorts; models adjusted for age, geographic region, and pre-index clinical (comorbidities, bone/ brain metastases, docetaxel). Results: Among ABI (n=1,095) and ENZ (n=421) cohorts, baseline SREs were similar: 82.57% (n=903) and 79.57% (n=335) respectively had no baseline SREs (P=0.192).

Follow-up incidence rates for SREs were higher for the ENZ vs. ABI patients (incidence rate ratio 1.27, P=0.044). Adjusted Cox proportional hazards analysis found a higher hazard of SREs for ENZ vs. ABI (HR: 1.34; 95% confidence limits: 1.06, 1.69; P=0.015) [7].

These findings demonstrate that patients with mCRPC who were initiated on ABI had better SRE outcomes than those initiated on ENZ who had a 34% higher risk of SREs. This anaysis provides insights on "real-world outcomes” of patients with mCRPC who are treated with ABI versus ENZ.  

References: 

[1] Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12:6243s-9s. http: //dx.doi.org/10.1158/1078-0432.CCR-06-0931. 

[2] Langer C, Hirsh V. Skeletal morbidity in lung cancer patients with bone metastases: demonstrating the need for early diagnosis and treatment with bisphosphonates. Lung Cancer 2010;67:4-11. http://dx.doi.org/10.1016/j.lungcan.2009.08.020.  S0169-5002(09) 00484-X. 

[3] Coleman RE. Skeletal complications of malignancy. Cancer 1997; 80:1588-94. doi: 10.1002/(SICI)1097-0142(19971015)80:8þ<1588:: AID-CNCR9>3.0.CO;2-G. 

[4] Coleman RE. Bisphosphonates: clinical experience. Oncologist 2004;9:14-27. doi: 10.1634.theoncologist.9-90004-14. 

[5] Harris K, Chow E, Zhang L, et al. Patients’ and health care professionals’ evaluation of health-related quality of life issues in bone metastases. Eur J Cancer 2009;45:2510-8

[6] Saylor PJ, Armstrong AJ, Fizazi K, et al. New and emerging therapies for bone metastases in genitourinary cancers. Eur Urol 2013;63:309-20. http://dx.doi.org/10.1016/j.eururo.2012.10.007.

[7] Nicole Engel-Nitz, Ajay S. Behl, Cori Blauer-Peterson, Nancy Ann Dawson.  Real-world skeletal related events (SREs) associated with oral treatments in patients with metastatic castration-resistant prostate cancer (mCRPC). 2016 ASCO Annual Meeting, Chicago, IL. Available at: http://meetinglibrary.asco.org/print/2395461