Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis

Brasso, Klaus; Thomsen, Frederik Birkebæk; Schrader, Andres Jan; Schmid, Sebastian; Lorente, David; Retz, Margitta; Merseburger, Axel S.; Klot, Christoph A. von; Boegemann, Martin; Bono, Johann S. de

doi:10.1016/j.eururo.2014.07.028

Cited by 101 publications

(77 citation statements)

References 23 publications

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“…In another pooled multicenter cohort of patients with mCRPC and prior abiraterone and chemotherapy with docetaxel, enzalutamide therapy induced a PSA decline $ 50% in only 18% of the patients (19). Furthermore, Noonan et al reported a PSA decline $ 50% in only 1 of 30 (3%) patients treated with abiraterone after progression under enzalutamide (20).…”

Section: Discussionmentioning

confidence: 99%

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

et al. 2016

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177 Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castrationresistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177 Lu-PSMA-617 in a large cohort of patients. Methods: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177 Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline $ 50% from baseline to at least 2 wk after the start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177 Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

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Section: Discussionmentioning

confidence: 99%

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

et al. 2016

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“…Brasso et al first reported that patients who had >30% or 50% of PSA decline with enzalutamide had longer OS compared with patients who had no such PSA decline (11.4 vs 7.1 months, P = 0.001, and 12.6 vs 7.4 months, P = 0.007, respectively). 35 Subsequently, several studies reported the clinical value of the PSA decline within 4 weeks from the initiation of ASI (Table 4). 35,[47][48][49][50] Importantly, all these studies showed that patients who did not respond to ASI within 4 weeks had a poor prognosis for not only PFS, but also OS, implying that other agents, such as taxanes, should be considered for these patients rather than trying another ASI.…”

Section: Prognostic Factors To Assist Decision-makingmentioning

confidence: 99%

“…[31][32][33][34][35][36][37][38] Data seem to show a blunted effect of each after the use of the other, suggesting cross-resistance. It remains unclear which patients benefit from one agent as the first agent compared with the other.…”

Section: Sequential Therapy Using Asismentioning

confidence: 99%

Current treatment strategies for advanced prostate cancer

et al. 2017

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During the past decade, treatment strategies for patients with advanced prostate cancer involving stage IV (T4N0M0, N1M0 or M1) hormone-sensitive prostate cancer and recurrent prostate cancer after treatment with curative intent, as well as castration-resistant prostate cancer, have extensively evolved with the introduction and approval of several new agents including sipuleucel-T, radium-223, abiraterone, enzalutamide and cabazitaxel, all of which have shown significant improvement on overall survival. The appropriate use of these agents and the proper sequencing of these agents are still not optimized. The results of several recently reported randomized controlled trials and retrospective studies could assist in developing a treatment strategy for advanced prostate cancer. In addition, prospective studies and molecular characterization of tumors to address these issues are ongoing.

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“…Currently, the only available data on sequencing are from a number of small, often retrospective, analyses in heavily pretreated patients who took part in compassionate use programs. These analyses evaluated patients with mCRPC who received enzalutamide treatment after progressing on chemotherapy and abiraterone [Badrising et al 2014;Bianchini et al 2014;Brasso et al 2014;Schmid et al 2014;Schrader et al 2014;Thomsen et al 2014] and, conversely, those receiving abiraterone treatment after progressing on chemotherapy and enzalutamide [Loriot et al 2013;Noonan et al 2013]. Evaluation of PSA-based outcomes and survival criteria in these analyses showed modest clinical activity with both scenarios in heavily pretreated patients with mCRPC and highlighted the need for further systematic investigation of treatment sequencing, as well as clarification of the possible mechanism of cross-resistance between enzalutamide and abiraterone.…”

Section: Us and Eu Treatment Guidelinesmentioning

confidence: 99%

An update on enzalutamide in the treatment of prostate cancer

Merseburger

Haas

Klot

2014

Therapeutic Advances in Urology

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Abstract:Enzalutamide is an oral androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway. In the randomized phase III AFFIRM study, significant improvements in survival versus placebo were observed when enzalutamide was used as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) following prior treatment with docetaxel. Additional benefits included significant delay in time to first skeletal-related event, and improvement in several measures of pain and health-related quality of life. Treatment effects were consistent across all prespecified subgroups. The phase III PREVAIL study evaluated enzalutamide versus placebo in patients with mCRPC who had not received chemotherapy. Enzalutamide significantly decreased the risk of radiographic progression and death. There were also significant improvements in all secondary and prespecified exploratory endpoints, including delayed initiation of chemotherapy, reduction in risk of first skeletal-related event and a high percentage of patients with objective response compared with placebo. Enzalutamide was also studied in hormone naïve patients (as monotherapy) in a small, open-label phase II study in patients with prostate cancer who were eligible for androgen-deprivation therapy. A prostate-specific antigen (PSA) response, defined as ⩾80% decline in PSA level from baseline at week 25, was achieved in 92.5% of patients. Long-term follow up is ongoing. Despite differences between these three trials, enzalutamide displayed a favorable safety profile in all three patient populations. Similar rates of adverse events between the enzalutamide and placebo groups were observed in AFFIRM and PREVAIL, with fatigue, diarrhea, back pain and hot flashes being more common with enzalutamide than with placebo. Hypertension was reported at a higher rate in the enzalutamide group than in the placebo group in PREVAIL. Breast-related disorders associated with enzalutamide treatment were also reported in the Monotherapy trial. Few seizures were reported in any trial. Enzalutamide is being studied in several early disease state populations.

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Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis

Cited by 101 publications

References 23 publications

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

Current treatment strategies for advanced prostate cancer

An update on enzalutamide in the treatment of prostate cancer

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Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis

Cited by 101 publications

References 23 publications

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

Current treatment strategies for advanced prostate cancer

An update on enzalutamide in the treatment of prostate cancer

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Product

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German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients