Treatment patterns and survival in metastatic castration‐sensitive prostate cancer in the US Veterans Health Administration

Abstract

Background Limited real‐world data exist on treatment patterns and outcomes in patients with metastatic castration‐sensitive prostate cancer (mCSPC). Methods A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013–March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT‐only (± <90‐day nonsteroidal anti‐androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time‐to‐progression to metastatic castration‐resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. Results Of 1395 patients, 874 (63%) received ADT‐only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT‐only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration‐resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT‐only. Conclusions Most patients with mCSPC initiating ADT received ADT‐only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT‐only. These data in real‐world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

Does Clinical Evidence of Heterogeneity Impact Treatment Selection? A Case Study of Abiraterone for Metastatic Prostate Cancer

“…Previous studies analyzing real-world data have described treatment patterns for mHSPC. Two recently published studies by Ryan et al 35 and Freedland et al 36 showed an increase in AAP usage since 2017, which agrees with the general trend found in our study. However, we found that overall usage of AAP was slightly lower in our cohort.…”

“…There are 2 possible explanations for this discrepancy. First, Ryan et al 35 reported their uptake rate as the proportion of men receiving AAP in their sample stratified by the year of first metastasis diagnosis, and Freedland et al 36 reported the proportion of AAP use among all men receiving therapy in the year they evaluated. Moreover, both studies focused on individuals with insurance coverage, which differs from our cohort that includes both insured and uninsured men.…”

Androgen receptor genomic alterations and treatment resistance in metastatic prostate cancer

“…First, nearly all studies to date were conducted in patient populations that did not receive ARPI in the mCSPC setting (i.e., they received ADT monotherapy or in combination with taxanes). Potent ARPI are increasingly used in patients with mCSPC, 9 and new studies will need to assess the prognostic implication of AR amplification detection in a post‐ARPI‐treated mCRPC population. Second, detection of AR amplification in liquid biopsy requires that a sample contains relatively high levels of ctDNA or CTCs.…”

“…Second, emerging radionuclide therapies (e.g., 177 Lutetium [Lu]‐prostate‐specific membrane antigen [PSMA]) 4,5 or genomic biomarker‐directed therapies (e.g., poly [ADP‐ribose] polymerase [PARP] inhibitors) 6,7 are further crowding an already complex treatment landscape. Third, although recent phase III clinical trial data supports ARPI use early in the disease course and in combination with taxanes, 8 real‐world evidence suggests that the majority of men with metastatic castration‐sensitive prostate cancer (mCSPC) continue to be treated with androgen deprivation therapy (ADT) alone 9 . Together, these challenges mean that treatment patterns frequently differ geographically and between similarly presenting patients.…”

“…castration-sensitive prostate cancer (mCSPC) continue to be treated with androgen deprivation therapy (ADT) alone. 9 Together, these challenges mean that treatment patterns frequently differ geographically and between similarly presenting patients. There is an urgent need for prognostic and predictive biomarkers to guide individual patient systemic therapy selection.…”