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ASCO 2019 Annual Meeting

ASCO 2019: Treatment Sequence in Elderly Metastatic Castration-Resistant Prostate Cancer Patients in a Prospective Cohort Study

Chicago, IL (UroToday.com) There are two primary classes of front-line treatment options for patients with mCRPC – either second generation androgen antagonists (enzalutamide or abiraterone) or chemotherapy (docetaxel or cabazitaxel). Many factors impact the choice of therapy including prior therapies (if the patient had already progressed on abiraterone in the mCSPC setting, enzalutamide may not be effective), patient performance status (could the patient tolerate chemotherapy?), and disease burden (does this patient have widespread visceral disease?). For elderly patients over the age of 75, it is unknown what the optimal sequence of therapy should be. This study examines the geriatric population of 75-year-olds with metastatic castration-resistant prostate cancer (mCRPC) and the outcomes following treatment with docetaxel or abiraterone/enzalutamide.

This abstract provides data on 419 patients from the prospective PROREPAIR-B cohort study (NCT03075735), a multicenter observational cohort study of unselected patients with mCRPC and unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent. Of these patients, 32.7% were ≥75 years old. Of the elderly population, the majority received abiraterone or enzalutamide (64%) and 35% of patients received docetaxel. 121 patients have progressed on first-line therapy and 25% of these patients did not go on to receive second-line therapy. Of the 91 patients who went on to receive second-line therapy, the most common option was abiraterone/enzalutamide (31.4%), followed by docetaxel (30.6%), cabazitaxel (7.4%), and radium-223 (5.8%).

Given that this is not a randomized study, it is not surprising that the patients who received front line docetaxel had more poor risk features than those receiving abiraterone/enzalutamide, including higher rates of visceral metastases (22.9% vs 5.7%), higher alkaline phosphatase (68.8% vs 43.2%), and lower hemoglobin (12.5% vs 3.4%). Thus, it is also not surprising that the progression-free survival (PFS) based on PCWG2 criteria was longer for the patients receiving abiraterone/enzalutamide compared with docetaxel (9.6 months vs 8.3 months, HR 0.52, p=0.001).

Interestingly, despite a difference in PFS, there was no difference in overall survival (OS) between the two groups of patients (28.2 months vs 24.8 months, HR1.18, p=0.474), and this held up in the multivariate model which included Gleason, initial stage at diagnosis, visceral metastases, alkaline phosphatase, LDH, HGB, albumin, and ECOG performance status.

This study demonstrated no difference in overall survival for patients who were treated with docetaxel compared with abiraterone/enzalutamide for patients ≥75 years old. While multivariate analysis was conducted to help control for patient factors, this was not a randomized study so comparisons between the two treatment groups are imperfect. However, this does demonstrate that for elderly patients with poor-risk features, docetaxel chemotherapy is a reasonable choice and should be considered early on in robust patients, especially since 25% of patients will not go on to receive second-line therapy in this setting and it will be easier to tolerate abiraterone/enzalutamide in the second line setting.

Presented by: Maria Jose Mendez-Vidal, MD, Department of Oncology, Hospital Universitario Reina Sofía, Córdoba, Spain

Written by: Jason Zhu, MD, Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA