EURURO Vol. 71 No. 4

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toxicity profile of AA may allow a greater proportion of
mCRPC patients, especially older men, to receive effective
mCRPC medical therapy. Treatment patterns are important
for older patients with mCRPC for several reasons. In
comparison to younger patients, elderly men are more
likely to present with advanced disease . Although age-
related changes may affect the risk of toxicities, age alone
should not prevent patients from deriving benefit from
cancer treatment . Indeed, the clinical benefit of AA
and enzalutamide among elderly patients with mCRPC has
been demonstrated in post hoc analyses for randomized,
double-blind phase 3 trials .
There are several important limitations to the analysis.
Subsequent therapy and treatment patterns were evaluated
retrospectively, and no specific end points were defined;
investigators were instructed to follow PCWG2 criteria.
Since patients were under routine clinical care and no
longer on trial, PSA data were not available for most patients
to confirm PSA response or progression data, and thus there
was a high censoring rate. Among the 261 AA patients who
received docetaxel as FST, post-trial baseline and post-
baseline PSA values were not available for 161 men. Thus,
the confirmed PSA response was limited to the 100 patients
with baseline and post-baseline PSA values available, which
may have introduced selection bias. For example, patients
who progressed rapidly on docetaxel may be under-
represented in the analysis compared to patients who
had a more favorable clinical course and possibly more
folllow-up PSA data available.
5. Conclusions
This post hoc analysis for chemotherapy-naı¨ve patients
with mCRPC who experienced disease progression on AA
suggests that docetaxel has meaningful antitumor activity
as FST. While acknowledging the limitations of a retrospec-
tive analysis, our observations suggest that docetaxel may
be considered for patients with mCRPC who progress on AA
treatment. A substantial proportion of older patients with
mCRPC who progressed on AA received no subsequent
therapy with drugs approved for mCRPC. This may be
explained by a broader group of mCRPC patients considered
eligible for first-line AA therapy but not considered
candidates for other subsequent mCRPC treatments such
as docetaxel after progression on AA. Taken together, these
data indicate that further assessment of subsequent therapy
and treatment patterns following AA treatment for mCRPC
is warranted, particularly among older patients.
Presented in part at the 2016 Genitourinary Cancers
Symposium (ASCO GU), January 6–9, 2016, San Francisco,
CA, USA (abstract 168); the 2015 Genitourinary Cancers
Symposium (ASCO GU), February 26–28, 2015, Orlando, FL,
USA (abstract 184); and the 2015 European Association of
Urology (EAU) Congress, March 20–24, 2015, Madrid, Spain
(abstract 668).
Author contributions: Johann S. de Bono 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: de Bono, Flaig, De Porre, Kheoh, Li, Todd, Griffin.
Acquisition of data: de Bono, Flaig, Saad, Shore, Rathkopf, Smith, Fizazi,
Mulders, North, Small, Ryan.
Analysis and interpretation of data: de Bono, Flaig, De Porre, Kheoh, Li,
Todd, Griffin.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All
authors.
Statistical analysis: Kheoh, Li.
Obtaining funding: De Porre.
Administrative, technical, or material support: De Porre.
Supervision: All authors.
Other: None.
Financial disclosures: Johann S. de Bono 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, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: Johann S. de
Bono is a consultant/advisor to and has received honoraria from Johnson
& Johnson. Matthew R. Smith is a consultant/advisor to and has received
research funding from Janssen. Fred Saad is a consultant/advisor to and
has received honoraria and research funding from Astellas and Janssen.
Dana E. Rathkopf provides uncompensated research funding for Celgene,
Janssen/Johnson & Johnson, Medication/Astellas, Millenium, and Novar-
tis. She is also a consultant/advisor to Johnson & Johnson. Peter F.A.
Mulders and Eric J. Small have nothing to disclose. Neal D. Shore is a
consultant/advisor to Amgen, Astellas, Bayer, BNI, Dendreon, Ferring,
Janssen, Medivation, Sanofi, Takeda, and Tolmar. Karim Fizazi is a
consultant/advisor to and has received honoraria from Janssen. Peter De
Porre, Thian Kheoh, Jinhui Li, and Mary B. Todd are employees of Janssen
Research and Development and hold stock in Johnson & Johnson. Charles
J. Ryan has received honoraria from Janssen. Thomas W. Flaig is a
consultant/advisor to GTx; has received honoraria from BN Immu-
noTherapeutics and GTx; receives research funding fromAmgen, Aragon,
Astellas, AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, Cougar
Biotechnology, Dendreon, Exelixis, GlaxoSmithKline, GTx, Janssen
Oncology, Lilly, Medivation, Novartis, Pfizer, Roche/Genentech, Sanofi,
Sotio, and Tokai; and holds stock in Aurora Oncology.
Funding/Support and role of the sponsor: This work was supported by
Janssen Research & Development (formerly Ortho Biotech Oncology
Research & Development, Cougar Biotechnology Unit). The sponsor
played a role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, and approval of the manuscript.
Acknowledgments: The authors thank Thomas W. Griffin for his critical
review of the analyses. Writing assistance was provided by Ann Tighe of
PAREXEL and was funded by Janssen Global Services LLC.
Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at
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