Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer
Mohamed E. AhmedMatthew S LeeAhmed M. MahmoudVidhu B. JoshiAjay GopalakrishnaRaevti BoleRimki HaloiA. Tuba KendiMichael S. BoldAlan H. BryceR. Jeffrey KarnesEugene D. KwonDaniel S ChildsJack R. Andrews
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Enzalutamide
Clinical endpoint
Univariate analysis
Abiraterone acetate
Introduction. In recent years, due to the progressive increase in the prevalence of castration-resistant prostate cancer (CRPC), the question of the sequence of prescription drugs is becoming more acute. Objective is to compare the effectiveness of various regimens of treatment of CRPC with the use of abirateron acetate and docetaxel. Materials and methods. The analysis included 83 patients with CRPC, which were divided into 2 groups depending on the sequence of appointment of abiraterone acetate and docetaxel. Results. Differences in the level of 2-year survival were statistically insignificant (73,2 % in the 1st group, 69 % in the 2nd group), and 3-year survival significantly differed: in the 1st group – 29,3 %, in the 2nd group – 16,7 % (p <0.05). Due to the short duration of the analysis, 5-year survival was not evaluated. The average value of overall survival in the appointment of the first docetaxel, then abiraterone acetate was 32 months, with the reverse regimen (abiraterone acetate, then docetaxel) – 27 months (p = 0.01). Conclusion . The scheme with the appointment of the first docetaxel, then abiraterone acetate is more effective from the point of view of affect on overall and 3-year survival in patients with CRPC.
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Enzalutamide and abiraterone acetate are novel drugs for the treatment of castration resistant prostate cancer (CRPC). These agents clearly demonstrated improvements in PFS and OS in patients with CRPC in large randomized Phase III trials. However, the problems exist such as side effects, PSA flare, treatment biomarkers and sequence of the treatment. Further research is necessary to determine the optimal sequence of the treatment or the optimal combination approach with both enzalutamide and abiraterone acetate. It is also necessary to find predictive factors (clinical or molecular) to assist the clinician in making better treatment decisions in an individualized manner.
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In the sentence beginning 'After adjusting for age...' in this article, the value of upper CI limit '0.84' should have read '0.94'.In the sentence beginning 'Unlike the overall population...' in this article, the value 'n = 700' should have read 'n = 786'.In the sentence beginning 'Nearly half (46,5%)...
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<p>Supplementary Fig 2 . Analysis of survival by baseline median alkaline phosphatase across the two studies using the study-specific median.</p>
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BACKGROUND The efficacy of and overall survival associated with metastatic castration-resistant prostate cancer (CRPC) treatments rely on patients' consistent adherence to the recommended dosage regimens. OBJECTIVES To evaluate treatment patterns and patient adherence to abiraterone acetate or enzalutamide therapy in real-world practice, and to examine the factors that may be associated with medication dose reduction in patients with metastatic CRPC. METHODS Retrospective analyses were conducted using the Truven Health MarketScan research databases among patients with metastatic CRPC who initiated treatment with abiraterone acetate or enzalutamide between October 1, 2012, and December 31, 2014 (index date). The patients were followed for up to 12 months, and their baseline characteristics were assessed during the 6 months before the index date. Medication adherence was measured at 3, 6, 9, and 12 months postindex using medication possession ratios (MPRs), and dose reduction was measured using refill gaps and relative dose intensity over the entire observation period. Kaplan-Meier survival analyses and Cox proportional hazards models were used to assess the association between the initial treatment and the risk for dose reduction. RESULTS The study included 2591 and 807 patients who initiated treatment with abiraterone acetate and enzalutamide, respectively. At 6, 9, and 12 months postindex, the patients who initiated abiraterone acetate had higher MPRs than the patients who initiated enzalutamide. In addition, the patients who initiated abiraterone acetate had lower Kaplan-Meier rates of dose reduction across 4 measurements for dose reduction. All hazard ratios for treatment (abiraterone acetate vs enzalutamide) were significantly lower than 1 (range, 0.57-0.80), indicating a lower risk for dose reduction associated with abiraterone acetate. CONCLUSION Patients who initiated abiraterone acetate therapy had higher medication adherence and lower risk for dose reduction than those who initiated enzalutamide therapy. Improved medication adherence may be associated with longer duration of treatment, which in turn may lead to better survival. Further research is needed to assess the potential effect of medication adherence on the overall survival of patients with metastatic CRPC.
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<p>Supplementary Data for Antonarakis et al</p>
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<p>Supplementary Fig 3 In vivo cellular and humoral responses through 52 weeks are illustrated here.</p>
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<div>AbstractPurpose:<p>We present long-term outcomes from 2 randomized studies [STAMP (with abiraterone, NCT01487863) and STRIDE (with enzalutamide, NCT01981122)] that were performed to study the impact of sequential or concurrent administration of androgen receptor–targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC).</p>Patients and Methods:<p>Sipuleucel-T was administered per current prescribing information. Results from STRIDE are presented together with updated STAMP results. Survival status of patients was updated using demographic information to query the National Death Index (NDI). Kaplan–Meier methodology was used to analyze survival.</p>Results:<p>Updated data reduced patient censoring in each study compared with the original analyses; the 95% confidence intervals (CIs) for OS are now estimable. Updated median OS (95% CI) is 33.3 (24.1–40.7) months for STAMP and 32.5 (26.0–45.1) months for STRIDE. There was no notable impact on median OS [HR, 0.727 (0.458–1.155); <i>P</i> = 0.177, reference = STRIDE]. OS with sequential administration was similar to concurrent administration [NDI update: HR, 0.963 (0.639–1.453); <i>P</i> = 0.845, reference = concurrent arm]. Sipuleucel-T potency, measured as antigen-presenting cell (APC) activation, was higher in subsequent infusions compared with the first infusion. Humoral responses (IgG + IgM antibody titers) to PA2024 and prostatic acid phosphatase were significantly elevated versus baseline. No new safety signals were observed.</p>Conclusions:<p>Median OS was consistent regardless of whether the agents were administered sequentially or concurrently, including after NDI update. Results suggest that sipuleucel-T induces an immunologic prime-boost effect after initial sipuleucel-T exposure, even when combined with ARTAs.</p></div>
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PurposeThe purpose of this study was to examine, using a US electronic medical records (EMR) database, the clinical characteristics and real-world treatment sequences in men with advanced prostate cancer who initiated treatment with abiraterone acetate or enzalutamide.MethodsThis retrospective, observational study evaluated adult male patients with a diagnosis of prostate cancer (International Classification of Diseases, Ninth Revision, Clinical Modification code 185) in the EMR database between July 1, 2011, and March 31, 2014, who had initiated first-line treatment with abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014. The first record for a patient initiating abiraterone acetate or enzalutamide was the index date. Patients had 6 months of pre-index medical record history and a variable length follow-up period, extending from the index date to the end of medical record data availability or date of the end of the study (March 31, 2014). The sequence of first- and second-line therapies for advanced prostate cancer therapy was reported.FindingsA total of 809 patients met study inclusion and exclusion criteria. This study found that the majority of patients who initiated treatment with either abiraterone acetate or enzalutamide between September 1, 2012, and March 31, 2014, received a single line of therapy (72%); abiraterone acetate was the most common first-line treatment (74% of first-line patients). A subset of patients treated first-line with either abiraterone acetate or enzalutamide were transitioned to an oral second-line agent (17% of first-line abiraterone acetate–treated patients transitioned to second-line enzalutamide, and 16% of first-line enzalutamide-treated patients transitioned to second-line abiraterone acetate). Chemotherapy with docetaxel was also a commonly observed second-line treatment selection, occurring in 8% of first-line abiraterone acetate–treated patients and in 7% of first-line enzalutamide-treated patients.ImplicationsThis EMR study is among the first to present evidence of US physician practice prescribing patterns regarding initiation of oral antineoplastic agents and use of subsequent therapies in patients with advanced prostate cancer.
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