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.

Metastatic castration-resistant prostate cancer (mCRPC) is the ultimately lethal form of prostate cancer. Docetaxel chemotherapy was the first life-prolonging treatment for mCRPC; however, the standard maximally tolerated dose (MTD) docetaxel regimen is often not considered for patients with mCRPC who are older and/or frail due to its toxicity. Low-dose metronomic chemotherapy (LDMC) is the frequent administration of typically oral and off-patent chemotherapeutics at low doses, which is associated with a superior safety profile and higher tolerability than MTD chemotherapy. We conducted a systematic literature review using the PUBMED, EMBASE, and MEDLINE electronic databases to identify clinical studies that examined the impact of LDMC on patients with advanced prostate cancer. The search identified 30 reports that retrospectively or prospectively investigated LDMC, 29 of which focused on mCRPC. Cyclophosphamide was the most commonly used agent integrated into 27/30 (90%) of LDMC regimens. LDMC resulted in a clinical benefit rate of 56.8 ± 24.5% across all studies. Overall, there were only a few non-hematological grade 3 or 4 adverse events reported. As such, LDMC is a well-tolerated treatment option for patients with mCRPC, including those who are older and frail. Furthermore, LDMC is considered more affordable than conventional mCRPC therapies. However, prospective phase III trials are needed to further characterize the efficacy and safety of LDMC in mCRPC before its use in practice.

117 Background: Ra233 is a well-tolerated, bone-seeking alpha emitter that prolongs the survival of men with mCRPC. Since there is a lack of validated biomarkers useful for disease monitoring during Ra223 therapy, we sought to characterize prostate-specific antigen (PSA) response patterns within a retrospective cohort study of real-world Ra223 treatment in four cancer centres across Ontario. Methods: Of 198 patients (pts) overall, 64 were not included due to incomplete data. The remaining 134 pts were grouped into (i) early PSA responders with a ≥30% PSA decrease (PSA30) within 12 weeks of treatment start, (ii) pts with an initial PSA flare followed by decreasing PSA, and (iii) non-responders. We analyzed the overall survival (OS) of these three cohorts using the Kaplan-Meier method and log-rank testing. Results: PSA30 responses were rare (n = 11; 8.2%), PSA flares were seen in 20.2% of pts (n = 27), but the majority of pts did not achieve a PSA response (n = 96; 71.7%). Of the pts identified as having a PSA flare, 11/27 (40.7%) presented with a post-flare PSA decrease below baseline, whereas in 16/27 (59.3%) the PSA decreased below the flare peak but not below baseline. 5/27 (18.5%) pts with a PSA flare achieved a PSA30. The median OS was not reached, 15.8 months and 14.7 months in responders, flare pts and non-responders, respectively (p > 0.05). Similarly, one year OS was 90.9%, 67.7% and 63.9% in responders, flare pts and non-responders. Conclusions: PSA flares are seen in one fifth of men undergoing Ra223 therapy for mCRPC. Despite delayed PSA declines of varying degrees, the survival of PSA flare pts is comparable to men without any PSA decline.