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LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p 0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p 0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.

Corticosteroids have been used to mitigate mineralocorticoid-related effects and restore sensitivity to abiraterone acetate. Corticosteroids may also mediate glucocorticoid receptor or mutated androgen receptor activation and adversely influence outcome.This post hoc exploratory analysis investigated whether baseline corticosteroids were an independent prognostic factor and its level of contribution in the presence of other prognostic factors for overall survival (OS) in study COU-AA-301.COU-AA-301 was a randomised study of abiraterone plus prednisone versus prednisone in metastatic castration-resistant prostate cancer patients after docetaxel.Patients were randomised 2:1 to abiraterone 1000 mg plus prednisone 5mg by mouth twice daily versus prednisone.Association of OS with baseline corticosteroids was determined by univariate and multivariate Cox models.At study entry, 33% of patients received corticosteroids, had worse disease characteristics (p0.05 except liver metastases), and were more likely to have testosterone levels below the median (odds ratio: 2.92; chi-square p0.0001). Associations between prostate-specific antigen response as well as circulating tumour cell decline and higher baseline androgen levels were demonstrated. Patients taking baseline corticosteroids had inferior OS in univariate analysis (hazard ratio: 1.48; p0.0001); however, in multivariate stepwise selection modelling, baseline corticosteroids did not add substantially to the model. This analysis is limited as a retrospective analysis and restricted to patients after docetaxel.In the COU-AA-301 study, baseline corticosteroids were associated with adverse prognostic features, inferior OS, and lower baseline androgen levels but did not add substantial information to the final prognostic model. Thus in these data from study COU-AA-301, concurrent baseline corticosteroids did not have an independent impact on OS.Baseline corticosteroids did not adversely affect abiraterone clinical benefit in metastatic castration-resistant prostate cancer. Their use was associated with patients having worse disease characteristics.

Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naive mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P. The primary endpoint was the proportion of patients with a dose-limiting toxicity (DLT) between weeks 2 and 7. The recommended phase 2 dose (RP2D) was the highest safe combination of docetaxel plus AA + P. Prostate-specific antigen (PSA) changes and intensive pharmacokinetic parameters for each drug were evaluated. Docetaxel 75mg/m 2 + AA 1000mg + P 10mg was deemed the RP2D, with DLT in one of six patients. PSA declines from baseline of ≥50% and ≥90% were observed for 85.7% and 66.7% of patients, respectively. During median follow-up of 14.5 mo, eight patients had PSA progression and six had radiographic progression or died. Systemic exposure was comparable for docetaxel and abiraterone when given alone or in combination. Studies are ongoing to confirm the efficacy of potent androgen receptor–targeted therapy plus taxane in early mCRPC. Patient summary The combination of hormonal therapy and chemotherapy may improve outcomes in men with metastatic prostate cancer. This study demonstrates the ability to combine the hormonal therapy agent abiraterone acetate, plus prednisone, and the chemotherapy drug docetaxel with an acceptable side effect profile. A high rate of prostate-specific antigen decline was seen, but the study was small and additional research is needed before this becomes a standard approach.