Abstract
Background The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial. Objective To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone. Design, setting, and participants Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide. Outcome measurements and statistical analysis The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. Results and limitations We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8-9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) >30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p = 0.001 and 12.6 vs 7.4 mo; p = 0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS. Conclusions Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline >30% or 50%, respectively, with enzalutamide in this setting had longer survival. Patient summary Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.
| Original language | English |
|---|---|
| Journal | European Urology |
| Volume | 68 |
| Issue number | 2 |
| Pages (from-to) | 317-324 |
| Number of pages | 8 |
| ISSN | 0302-2838 |
| DOIs | |
| Publication status | Published - 01.08.2015 |
Funding
This study presents data from four European studies on compassionate-access enzalutamide for mCRPC patients progressing following docetaxel and abiraterone. We demonstrate that enzalutamide, when administered as a third-line treatment, has more modest antitumour activity than that reported in the AFFIRM trial. Nonetheless, patients who had a PSA decline >30% and 50% have superior survival and may benefit from this agent. With the increasing number of treatment options available for patients who have mCRPC, well-conducted studies determining the optimal treatment sequence or combination of these drugs are urgently needed to base future treatment algorithms on solid evidence. Author contributions: Klaus Brasso had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Brasso, Thomsen, Schmid, Merseburger, de Bono. Acquisition of data: Brasso, Thomsen, Schrader, Schmid, Lorente, Retz, Merseburger, von Klot, Boegemann, de Bono. Analysis and interpretation of data: Brasso, Thomsen, Schrader, Schmid, Lorente, Retz, Merseburger, von Klot, Boegemann, de Bono. Drafting of the manuscript: Brasso, Thomsen. Critical revision of the manuscript for important intellectual content: Schrader, Schmid, Lorente, Retz, Merseburger, von Klot, Boegemann, de Bono. Statistical analysis: Brasso, Thomsen. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Brasso. Other (specify): None. Financial disclosures: Klaus Brasso certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Klaus Brasso received consulting fees from Astellas, Bayer AG, and Sanofi-Aventis as well as lecture fees from Ferring and Sanofi-Aventis. Andres J. Schrader received consulting and lecture fees from Astellas Pharma GmbH, Janssen-Cilag GmbH, Pfizer GmbH, Bayer AG, GlaxoSmithKline, Novartis, Medac, Ipsen Pharma, and Sanofi-Aventis. Sebastian Schmid received lecture fees from Astellas Pharma GmbH and travel grants from GlaxoSmithKline GmbH & Co. KG. Margitta Retz received lecture fees and honoraria from Astellas Pharma GmbH, Janssen-Cilag GmbH, Pfizer GmbH, Bayer AG, and GlaxoSmithKline GmbH & Co. KG. Alex Merseburger received lecture fees and honoraria from Astellas Pharma GmbH, Janssen-Cilag GmbH, Novartis Pharma, Pfizer GmbH, Bayer AG, and GlaxoSmithKline GmbH & Co. KG. Martin Boegemann received lecture fees and honoraria from Astellas Pharma GmbH, Janssen-Cilag GmbH, Pfizer GmbH, Bayer AG, Teva GmbH, and GlaxoSmithKline GmbH & Co. KG. Johann de Bono received consulting fees from Ortho Biotech Oncology Research and Development (a unit of Cougar Biotechnology); consulting fees and travel support from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dendreon, Enzon, Exelixis, Genentech, GlaxoSmithKline, Medivation, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Supergen, and Takeda; and grant support from AstraZeneca and Genentech. Funding/Support and role of the sponsor: None. Appendix A
