Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

Abstract

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

Effect of Chemotherapy on Overall Survival in Contemporary Metastatic Prostate Cancer Patients

“…It is noteworthy, that the magnitude of the benefit in the current study, as well as in the study of Weiner et al, cannot be directly compared to the magnitude of survival benefit recorded in phase 3 trials for specific systemic approaches for metastatic prostate cancer (18,19). It is of note, that the magnitude of the survival benefit in most of phase 3 studies addressing overall survival in metastatic prostate cancer was greater than the magnitude recorded in our study, as well as that recorded in the study of Weiner et al and other small scale institutional studies (20)(21)(22).…”

“…It is of note, that the magnitude of the survival benefit in most of phase 3 studies addressing overall survival in metastatic prostate cancer was greater than the magnitude recorded in our study, as well as that recorded in the study of Weiner et al. and other small scale institutional studies ( 20 – 22 ).…”

Presence of CD133‐positive circulating tumor cells predicts worse progression‐free survival in patients with metastatic castration‐sensitive prostate cancer

“…Briones et al . studied the survival of mCSPC patients after receiving docetaxel or abiraterone combination therapy and found that age at diagnosis of mCSPC, PSA90 at 3 months, and LATITUDE risk classification are prognostic factors of PFS 18 …”

“…17 Briones et al studied the survival of mCSPC patients after receiving docetaxel or abiraterone combination therapy and found that age at diagnosis of mCSPC, PSA90 at 3 months, and LATITUDE risk classification are prognostic factors of PFS. 18 However, these traditional markers all have their own limitations. Gleason score mainly reflects the degree of malignancy of the primary lesion and cannot reflect tumor burden in the whole body of metastatic prostate cancer patients.…”

Assessment of androgen receptor signaling inhibitors therapy in metastatic hormone-sensitive prostate cancer

“…Based on a large randomize controlled trial, larger OS benefits were shown in abiraterone acetate and apalutamide treatment whereas enzalutamide was associated with a greater improvement in PFS. Moreover, large population retrospective studies have found several factors related to ARSI efficacy, including tumor volume, level of prostate specific antigen (PSA) at diagnostic, age and visceral metastasis 16 .…”