BACKGROUND\ud Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design.\ud METHODS\ud We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer).\ud RESULTS\ud A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events).\ud CONCLUSIONS\ud Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.

The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients.

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GC has received grants, research support or is coinvestigator in clinical trials by Bristol-Myers-Squibb, Celgene, Boehringer Ingelheim, Roche, Tigen Pharma, Iovance and Kite. GC has received honoraria for consultations or presentations by Roche, Genentech, BMS, AstraZeneca, Sanofi-Aventis, Nextcure and GeneosTx. GC has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T-cell expansion and engineering for T-cell therapy. GC receives royalties from the University of Pennsylvania. FH reports grants from Prostate Cancer Foundation, Bristol-Myers-Squibb, Accuray Inc, Bioprotect, and non-financial support from Roche ImFlame cooperative group, European Organization for Research and Treatment of Cancer (EORTC) chairman Gynecology Cancer Group. FH has received honoraria for consultations from

5005 Background: The TAX-327 study compared 3 weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 patients (pts) with metastatic hormone resistant prostate cancer (mHRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, PSA and quality of life for D3 when compared with M (Tannock et al, NEJM 2004;351:1502–12). Here we present the updated survival analysis. Methods: Investigators were asked to provide date of death or last follow up for all patients alive in August 2003. Results: By December 2007 data on 276 additional deaths were obtained (total 833 deaths, see Table ). The survival benefit of D3 as compared with M has persisted with extended follow up while D1 continues to show no significant survival advantage. More patients (17.9% and 16.7%) survived =3 years in the D3 and D1 arms compared to M (13.7%). Similar trends in survival between treatment arms were seen for pts above and below 65 years of age, for those with and without pain at baseline, and for those with baseline PSA above and below median value of 115ng/ml. Conclusions: The present analysis confirms previous findings that survival is significantly longer with D3 than with M. Survival update is ongoing. [Table: see text] No significant financial relationships to disclose.

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BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P 5.77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P 5.48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

on behalf of the TAX-327 investigators Abstract Purpose: The TAX-327 study randomized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel, weekly docetaxel, or mitoxantrone, each with prednisone. Experimental Design:We used theTAX-327 database to address (a) the relationship between quality of life (QoL) and pain; (b) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL; (c) the relationships between prostate-specific antigen (PSA) response, pain response, and QoL response; (d) the times at which these responses are first observed; and (e) whether PSA, pain, and/or QoL response predict for overall survival. Results: At baseline, 374 of 815 men assessed for QoL had major pain; of these, 92% had substantial impairment of QoL compared with 75% without major pain (P < 0.001). Men with minimal symptoms had prolonged survival (median, 25.6 months) compared with symptomatic patients (median, 17.1 months; P = 0.009); they were more likely to have initial deterioration of QoL if treated with weekly docetaxel. PSA response and pain response, but not QoL response, were independently associated with survival in landmark analysis. Median times to PSA and pain response were 44 and 27 days, respectively; some men had initial increase in serum PSA before subsequent decline. Conclusions: Symptoms other than pain contribute to impaired QoL in men with hormonerefractory prostate cancer. Those with minimal symptoms have prolonged survival. Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies. Early increases in serum PSA (up to 12 weeks) should be ignored when determining response or progression.Metastatic prostate cancer is an incurable disease and the goal of treatment is palliation. Hormonal treatment is effective initially, but after a variable time, prostate cancer progresses to a hormone-refractory state. Many men then receive chemotherapy with the goals of alleviating symptoms and prolonging survival. The TAX-327 study was a large international randomized trial, which compared the effectiveness of 3-weekly mitoxantrone and prednisone (M/P) with 3-weekly docetaxel and prednisone (D3/P) or weekly docetaxel and prednisone (D1/P) for men with hormone-refractory prostate cancer (1). The primary end point of the study was overall survival, whereas pain response, prostate-specific antigen (PSA) response, and quality of life (QoL) response were secondary end points. Men treated with docetaxel every 3 weeks with prednisone were found to have superior overall survival, pain response, PSA response, and QoL response when compared with those receiving mitoxantrone and prednisone (1).Here, we have examined the database from the TAX-327 study to provide an in-depth analysis of the relationships between PSA response, pain response, QoL response, and survival. We attempt to address the following questions: Materials and MethodsDetails of participants and their treatment are descri...