Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks

Abstract Purpose [177Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC). Here, we aimed to estimate the results of PSMA-RLT in terms of response, progression-free survival (PFS), and overall survival (OS) in patients receiving a highly standardized treatment regimen due to mCRPC. The toxicity of PSMA-RLT has also been evaluated. Patients and methods Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0–4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment. Results The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7–4563 μg/L, P < 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks, P < 0.0001) and OS (median survival not reached vs. 52 weeks, P < 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks, P < 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks, P = 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9–13.7 g/L vs. 4.8, range 1.5–12.3 g/L) decreased significantly, both P < 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed. Conclusion Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.

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Prediction of response and survival after standardized treatment with 7400 MBq 177Lu-PSMA-617 every 4 weeks in patients with metastatic castration-resistant prostate cancer

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05082-5 ◽

2020 ◽

Author(s):

Sazan Rasul ◽

Markus Hartenbach ◽

Tim Wollenweber ◽

Elisabeth Kretschmer-Chott ◽

Bernhard Grubmüller ◽

...

Keyword(s):

Prostate Cancer ◽

Median Survival ◽

Therapy Response ◽

Binary Logistic Regression ◽

Response To Therapy ◽

Castration Resistant Prostate Cancer ◽

Treatment Regimens ◽

Castration Resistant ◽

Kaplan Meier ◽

Standardized Treatment

Abstract Background and aims [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks. Patients and methods Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0–4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS). Results Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09–2.09) with an AUC of 0.68 (95% CI: 0.54–0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P < 0.05 (relative risk 1.51 and 0.79, 95% CI: 1.09–2.09 and 0.43–1.46), respectively. In comparison to patients with reduced basal Hb, patients with normal basal Hb levels lived significantly longer (median survival not reached vs. 89 weeks, P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT. Conclusion Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival.

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Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽

10.3390/cancers13102489 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2489

Author(s):

Sazan Rasul ◽

Tim Wollenweber ◽

Lucia Zisser ◽

Elisabeth Kretschmer-Chott ◽

Bernhard Grubmüller ◽

...

Keyword(s):

Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Free Survival ◽

Castration Resistant ◽

Kaplan Meier ◽

Node Metastases ◽

Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

Case Reports in Oncology ◽

10.1159/000447710 ◽

2016 ◽

Vol 9 (2) ◽

pp. 506-515

Author(s):

Vanita Noronha ◽

Amit Joshi ◽

Vamshi Krishna Muddu ◽

Vijay Maruti Patil ◽

Kumar Prabhash

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Castration Resistant ◽

Retrospective Data Analysis ◽

Grade 3 ◽

Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

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Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽

10.1159/000440942 ◽

2015 ◽

Vol 61 (1) ◽

pp. 23-31 ◽

Cited By ~ 4

Author(s):

Noriyoshi Miura ◽

Nozomu Tanji ◽

Yutaka Yanagihara ◽

Terutaka Noda ◽

Seiji Asai ◽

...

Keyword(s):

Prostate Cancer ◽

Low Dose ◽

Specific Antigen ◽

Progression Free Survival ◽

Hematological Toxicity ◽

Castration Resistant Prostate Cancer ◽

Gastric Bleeding ◽

Castration Resistant ◽

Analgesic Agents ◽

Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

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Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.tps4692 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. TPS4692-TPS4692 ◽

Cited By ~ 1

Author(s):

Mario A. Eisenberger ◽

Anne-Claire Hardy-Bessard ◽

Loic Mourey ◽

Paul N. Mainwaring ◽

Daniel Ford ◽

...

Keyword(s):

Prostate Cancer ◽

Progression Free Survival ◽

Phase Iii ◽

Hematologic Toxicity ◽

Castration Resistant Prostate Cancer ◽

Open Label ◽

Measurable Disease ◽

Previously Treated ◽

Grade 3 ◽

Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

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ARCHES: Efficacy of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5048 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5048-5048

Author(s):

Andrew J. Armstrong ◽

Russell Zelig Szmulewitz ◽

Daniel Peter Petrylak ◽

Jeffrey M. Holzbeierlein ◽

Arnauld Villers ◽

...

Keyword(s):

Prostate Cancer ◽

Radiographic Progression ◽

Progression Free Survival ◽

High Volume ◽

Castration Resistant Prostate Cancer ◽

Double Blind ◽

Prior Therapy ◽

Castration Resistant ◽

Secondary Endpoints ◽

Grade 3

5048 Background: ENZA has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ARCHES assessed the efficacy of ENZA with ADT in men with mHSPC, including pre-specified subgroups based on prior therapy. Methods: ARCHES, a multinational, double-blind, Phase 3 study (NCT02677896), randomized patients (pts) with mHSPC 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel (doce) use. Primary endpoint was radiographic progression-free survival (rPFS; centrally assessed radiographic progression or death within 24 weeks of treatment discontinuation). Secondary endpoints included time to initiation of new antineoplastic therapy and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n = 574) or PBO (n = 576). Overall, 63% had high-volume disease, 18% had prior doce, and 91% had prior ADT or orchiectomy (orch). Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); significant improvements in rPFS were also reported in prior treatment subgroups. Secondary endpoints improved with ENZA + ADT (Table), with no significant impact in time to deterioration in urinary symptoms. OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs. 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. PBO + ADT in men with mHSPC. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial information: NCT02677896. [Table: see text]

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Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.687 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 687-687 ◽

Cited By ~ 13

Author(s):

Andrew J. Armstrong ◽

Russell Zelig Szmulewitz ◽

Daniel Peter Petrylak ◽

Arnauld Villers ◽

Arun Azad ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Progression Free Survival ◽

High Volume ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Double Blind ◽

Secondary Endpoints ◽

Phase Iii Study ◽

Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

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The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.133 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 133-133

Author(s):

Yuchao Ni ◽

Jinge Zhao ◽

Junru Chen ◽

Guangxi Sun ◽

Sha Zhu ◽

...

Keyword(s):

Prostate Cancer ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Free Survival ◽

Castration Resistant ◽

Kaplan Meier ◽

Psa Progression ◽

Biochemical Progression ◽

First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

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Estrogen Receptor α and Aromatase Polymorphisms Affect Risk, Prognosis, and Therapeutic Outcome in Men with Castration-Resistant Prostate Cancer Treated with Docetaxel-Based Therapy

Molecular Endocrinology ◽

10.1210/mend.25.1.9996 ◽

2011 ◽

Vol 25 (1) ◽

pp. 195-195

Author(s):

Tristan M. Sissung ◽

Romano Danesi ◽

C. Tyler Kirkland ◽

Caitlin E. Baum ◽

Sandra B. Ockers ◽

...

Keyword(s):

Prostate Cancer ◽

Median Survival ◽

Single Agent ◽

Progression Free Survival ◽

Estrogen Receptor Α ◽

Interindividual Variation ◽

Castration Resistant Prostate Cancer ◽

Body Type ◽

Survival Difference ◽

Estrogen Synthesis

Abstract Context Reactive estrogen species cause genotoxicity and interfere with docetaxel-mediated tubulin polymerization resulting in shortened survival in men with castrate-resistant prostate cancer (CRPC). Objective We hypothesized that polymorphisms in estrogen synthesis and estrogen targets (i.e., CYP19 and ERα) would be linked to interindividual variation in CRPC risk, docetaxel response, and overall survival (OS) in men with CRPC. Materials and Methods Patients with CRPC (n = 115) treated with docetaxel, single-agent thalidomide (n = 42), or healthy controls (n = 289) were genotyped for the CYP19 R264C (rs700519) and the ERα PvuII T> C (rs2234693) and XbaI A> G (rs9340799) polymorphisms. Results Patients carrying two copies of ERα polymorphisms had shorter progression-free survival on docetaxel than other patients (median survival difference ≥3.1 months; P ≤ 0.036). When the analysis was limited to nonobese patients, the relationship between the ERα XbaI A> G polymorphism and PFS improved (median survival difference = 3.5 months; P = 0.0078). The CYP19 R264C variant was related to the duration of survival after docetaxel in patients who were > 70 years old (median survival difference = 10.6 months; P = 0.041). Both ERα polymorphisms were also associated with increases in CRPC risk [P ≤ 0.032; double variants vs. wild-type odds ratio (OR) ≥ 2.6], and the association with the ERα PvuII T> C also improved in those men who were < 70 years old (P = 0.0073; OR = 3.0). Conclusions This study demonstrates that estrogen-related genetic variation affects docetaxel clinical response and that this relationship is dependent on age and body-type in men with CRPC. Moreover, this study suggests ERα polymorphisms confer risk of developing prostate cancer, especially in men under 70 years of age.

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A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.55 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 55-55

Author(s):

Eleni Efstathiou ◽

Vasily J. Assikis ◽

Scott A. North ◽

John Showel ◽

Thomas E. Hutson ◽

...

Keyword(s):

Prostate Cancer ◽

Safety Profile ◽

Progression Free Survival ◽

Abiraterone Acetate ◽

Double Blind Study ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Double Blind ◽

Psa Response ◽

Grade 3

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]

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