commentary
Assessing the utility of cabazitaxel in mCRPC
Scott A. North, MD, FRCPC, MHPE
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada
Cite as: Can Urol Assoc J 2016;10(3-4):111-2. http://dx.doi.org/10.5489/cuaj.3721
It is important to note that patient selection is still critical
when using cabazitaxel or other cytotoxic agents. In the cur-
rent study, approximately one-third of individuals stopped
cabazitaxel for adverse events, but importantly, there were
no treatment-related deaths. It is notable that 30% received
prophylactic granulocyte colony-stimulating factor (GCSF) to
reduce the risk of severe and/or febrile neutropenia, some-
See related article on page 102.
aad et al report on the utility of cabazitaxel in men
with metastatic castration-resistant prostate cancer
8
S
(mCRPC) who either did or did not receive prior abir-
thing which was not done in the pivotal TROPIC trial. The
1
aterone acetate in addition to docetaxel chemotherapy.
These results were generated as part of an international,
expanded-access study, in which 61 Canadian men were
enrolled and for whom prior abiraterone exposure was
known for 60 subjects.
feasibility of this strategy will vary across jurisdictions in
Canada, where routine use of these agents is not always
available for individuals whose treatment intent is not cura-
tive. On the opposite side of the coin, however, a quarter
of individuals experienced improvements in their pain, and
overall, approximately 40% had a PSA response that was
not affected by prior abiraterone exposure. There were also
improvements noted in QoL, as measured by validated ques-
tionnaires. Thus, cabazitaxel in the post-docetaxel setting,
irrespective of prior abiraterone exposure, is an active agent,
but must be used in appropriately selected patients.
In recent years, the treatment landscape for mCRPC has
changed dramatically, with multiple life-prolonging agents
now available for treating the disease. Docetaxel was the first
agent shown to improve life expectancy, as demonstrated by
2
3
the TAX 327 and SWOG 9916 trials. Since then, survival
benefit in both the pre- and post-docetaxel setting has been
6,7
demonstrated for abiraterone acetate and enzalutamide,
4,5
It is comforting for clinicians managing these patients to
see that the efficacy of cabazitaxel is maintained in patients
with prior abiraterone exposure. With the plethora of new
agents available for managing this disease, many questions
have arisen as to how sequencing and multiple lines of ther-
apy may affect the utility of subsequent agents. As an example,
there were initial reports that the efficacy of docetaxel given
after prior abiraterone exposure may be significantly worse
8
and in the post-docetaxel setting, cabazitaxel and radium
9
2
23 have shown improved survival. Clinicians struggle
with how to optimally sequence these agents and are con-
cerned that as patients progress through multiple lines of
therapy, efficacy may be reduced, but toxicities will remain.
Abiraterone acetate was approved in Canada in July 2011
for men with mCRPC in the post-docetaxel setting and in May
10
2013 for the pre-docetaxel indication. Thus, in this report by
than reported in the original pivotal trials, but in other larger
reports, such as a post-hoc analysis of the COUGAR 302 trial,
Saad et al, we can assume that the 25 men treated with abir-
aterone all received it in the post-docetaxel setting. Patients
treated with cabazitaxel all enjoyed a good performance
status, but their clinical characteristics suggest their disease
was not indolent. Twenty-five percent of the population had
visceral metastases and 25% were treated with cabazitaxel
after rapid progression post-docetaxel (within three months).
Men who had received abiraterone tended to be older, not
surprisingly, often given the reluctance to treat men with
cytotoxic chemotherapy if they are older. However, the prior
use of abiraterone did not impact on the utility of cabazitaxel
in this population in terms of prostate-specific antigen (PSA)
response rate, quality of life (QoL) improvements, or safety.
11
this has not borne out. Thus, this report by Saad et al gives
us comfort that the use of cabazitaxel in a third-line setting
still has activity and tangible benefits for patients.
The authors note the limitations of their study due to
its non-randomized design, small sample size, and post-
hoc analysis. Also, there is no report on survival outcomes
for these patients so it is unknown whether the PSA and
QoL response rates have translated into improvements in
overall disease control and life expectancy for patients.
Nonetheless, in an incurable setting, improvements in QoL
are valuable for patients and justify the use of cabazitaxel
in this population.
CUAJ • March-April 2016 • Volume 10, Issues 3-4
2016 Canadian Urological Association
111
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