Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: U.S. Food and Drug Administration Drug Approval Summary

Kluetz, Paul G.; Ning, Yang‐Min; Maher, Virginia Ellen; Zhang, Lijun; Tang, Shenghui; Ghosh, Debasis; Aziz, Robeena; Palmby, Todd R.; Pfuma, Elimika; Zirkelbach, Jeanne Fourie; Mehrotra, Nitin; Tilley, Amy; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

doi:10.1158/1078-0432.ccr-13-2134

Cited by 58 publications

(44 citation statements)

References 15 publications

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“…In contrast, when used according to the adapted PCWG2 radiographic-progression criteria (4), bone scans have been shown to correlate strongly with survival in large trials of the use of enzalutamide and abiraterone in prostate cancer (5). This approach to radiographic progression assisted in identifying a positive effect on advanced prostate cancer and has been accepted by the U.S. Food and Drug Administration as a parameter with a potential impact on drug approval decisions (6).…”

Section: See Page 41mentioning

confidence: 99%

EXINI Quantitative Bone Scan Index: Expanded Utility for the Planar Radionuclide Bone Scan

Larson

2015

J Nucl Med

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Section: See Page 41mentioning

confidence: 99%

EXINI Quantitative Bone Scan Index: Expanded Utility for the Planar Radionuclide Bone Scan

Larson

2015

J Nucl Med

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“…However, this interim analysis of OS did not cross the O'Brien-Fleming boundary for statistical significance. Prespecified secondary endpoints such as the time to initiation of cytotoxic chemotherapy showed statistically significant improvements in favor of abiraterone acetate [8,9]. The totality of the findings, along with the established OS benefit in patients previously treated with docetaxel, justified the approval of abiraterone acetate for this indication.The results of the prespecified final analysis for OS were recently reported and showed a statistically significant improvement in OS for patients treated with abiraterone acetate compared with patients treated with placebo (HR, 0.81; 95% CI, 0.70-0.93; p 5 .003).…”

Section: Introductionmentioning

confidence: 93%

“…Compared with placebo plus prednisone, abiraterone acetate plus prednisone was associated with a 3.8-month prolongation of median OS (HR, 0.65; 95% CI, 0.54-0.77; p , .0001). In 2012, the indication was modified after FDA review of the results from a randomized, doubleblind, phase III trial in asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC and no visceral metastases [8,9]. The coprimary endpoints were OS and radiographic progression-free survival (rPFS).…”

Section: Introductionmentioning

confidence: 99%

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer

et al. 2015

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The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistantprostatecancer(mCRPC).Attheprespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.84).The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14-0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30-0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. The Oncologist 2015;20:960-966 Implications for Practice: This new approval expands the enzalutamide indication, allowing health care providers and patients to use enzalutamide for the treatment of metastatic castration-resistant prostate cancer either before or after cytotoxic chemotherapy.

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“…Three trials 12–14 have been terminated because positive interim results; the COU-302 trial with abiraterone/prednisone, the PREVAIL trial with enzalutamide, and the ALSYMPCA trial with radium-223. Both the ALSYMPCA and PREVAIL trials were terminated because SAP pre-defined end points were reached for overall survival and the OBF boundary was crossed.…”

Section: Practical Considerations and Early Terminations In Recent Trmentioning

confidence: 99%

“…As expected, the observed hazard ratio at the final analysis was higher (hazard ratio=0.80 for patients randomized to abiraterone acetate plus prednisone compared with patients randomized to placebo plus prednisone) than what was reported in the second interim analysis (hazard ratio=0.75). 16 In addition, several trials have been terminated early because survival was compromised including the trial with docetaxel/revlimid, the trial with docetaxel/GVAX, and the trial with docetaxel/vitamin D. 17–20 …”

Section: Practical Considerations and Early Terminations In Recent Trmentioning

confidence: 99%

Independent data monitoring committees: An update and overview

Halabi

2015

Urologic Oncology: Seminars and Original Investigations

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An Independent Data Monitoring Committee (IDMC) duty is to ensure that the interests of the patients entered on the trial are being well-served (i.e., that the risk-benefit ratio is appropriate) and that the scientific integrity of the trial is maintained during the interim between trial initiation and trial completion. Industry sponsors form IDMCs to ensure an independent assessment to assure that the study participants are not exposed to unnecessary or unreasonable risks as a consequence of their trial participation, and to ensure that the study is being conducted according to highest scientific and ethical standards. IDMCs are needed to analyze interim data for large randomized studies, in particular those that involve multiple sites and important clinical endpoints such as survival or disease progression. Ethical principles mandate that clinical trials begin with uncertainty as to which treatment is better (clinical equipoise). This uncertainty should be maintained during study conduct and analysis unless there is compelling data that emerges during the conduct of the trial. Group sequential statistical designs offer a mechanism to consider terminating a trial early and the results made public if the interim data become sufficiently compelling. Interim monitoring of safety and efficacy data is an integral part of modern clinical trials.

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Abiraterone Acetate in Combination with Prednisone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer: U.S. Food and Drug Administration Drug Approval Summary

Cited by 58 publications

References 15 publications

EXINI Quantitative Bone Scan Index: Expanded Utility for the Planar Radionuclide Bone Scan

EXINI Quantitative Bone Scan Index: Expanded Utility for the Planar Radionuclide Bone Scan

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer

Independent data monitoring committees: An update and overview

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