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Improved survival benefit with increased
docetaxel cycles in prostate cancer
JAMA Oncology
Take-home message
•
This study included 1059 patients with metastatic castration-resistant prostate cancer
(mCPRC) from the MAINSAIL trial and evaluated the relationship between number
of docetaxel cycles and overall survival. Regardless of lenalidomide treatment, receiving
eight or more docetaxel cycles was associated with significantly increased overall survival.
•
The study results indicate that continuing docetaxel chemotherapy improves clinical
benefit in patients with mCPRC, but further prospective studies are needed to validate
these findings.
Abstract
IMPORTANCE
The optimal total number of
docetaxel cycles in patients with metastatic
castration resistant prostate cancer (mCPRC)
has not been investigated yet. It is unknown
whether it is beneficial for patients to continue
treatment upon 6 cycles.
OBJECTIVE
To investigate whether the number
of docetaxel cycles administered to patients
deriving clinical benefit was an independent
prognostic factor for overall survival (OS) in a
post hoc analysis of the MAINSAIL trial.
DESIGN, SETTING, AND PARTICIPANTS
TheMAINSAIL
trial was a multinational randomized phase 3
study of 1059 patients with mCRPC receiving
docetaxel, prednisone, and lenalidomide (DPL)
or docetaxel, prednisone, and a placebo (DP).
Study patients were treated until progressive
disease or unacceptable adverse effects
occurred. Median OS was found to be inferior
in the DPL arm compared with the DP arm.
As a result of increased toxic effects with the
DPL combination, patients on DPL received
fewer docetaxel cycles (median, 6) vs 8 cycles
in the control group. As the dose intensity
was comparable in both treatment arms, we
investigated whether the number of docetaxel
cycles administered to patients deriving clinical
benefit on Mainsail was an independent
prognostic factor for OS. We conducted
primary univariate and multivariate analyses
for the intention-to-treat population. Additional
sensitivity analyses were done, excluding
patients who stopped treatment for reasons of
disease progression and those who received 4
or fewer cycles of docetaxel for other reasons,
minimizing the effect of confounding factors.
MAIN OUTCOMES AND MEASURES
Total number of
docetaxel cycles delivered as an independent
factor for OS.
RESULTS
Overall, all 1059 patients from the
Mainsail trial were included (mean [SD] age, 68.7
[7.89] years). Treatment with 8 or more cycles
of docetaxel was associated with superior OS
(hazard ratio [HR], 1.909; 95% CI, 1.660–2.194;
P<0.001), irrespective of lenalidomide treatment
(HR, 1.060; 95%CI, 0.924–1.215; P=0.41). Likewise,
in the sensitivity analysis, patients who received a
greater number of docetaxel cycles had superior
OS; patients who received more than 10 cycles
had a median OS of 33.0 months compared
with 26.9 months in patients treated with 8 to 10
cycles; and patients who received 5 to 7 cycles
had a median OS of 22.8 months (P<0.001).
CONCLUSIONS AND RELEVANCE
These findings
suggest that continuation of docetaxel
chemotherapy contributes to the survival
benefit. Prospective validation is warranted.
Association of survival benefit with docetaxel
in prostate cancer and total number of cycles
administered: a post hoc analysis of themainsail
study.
JAMA Oncol
2017 Jan 01;3(1)68-75, ES de
Morrée, NJ Vogelzang, DP Petrylak, et al
EDITOR’S NOTE
By Brian E Lewis
MD, MPH
T
he MAINSAIL study was a phase
III trial of 1059 men with mCRPC
who were randomised to either
docetaxel + prednisone + lenalidomide or
to docetaxel + prednisone + placebo. This
trial demonstrated inferiority for overall
survival in the lenalidomide arm. This
paper is a post hoc analysis evaluating the
number of cycles of docetaxel adminis-
tered and survival. The authors found that
the number of cycles of docetaxel admin-
istered, specifically less than eight or eight
or more cycles, was associated with over-
all survival independent of lenalidomide
use, with a hazard ratio of 1.9. Other
factors that were associated in the multi-
variate analysis included baseline LDH,
baseline haemoglobin, baseline albumin,
and baseline ECOG performance status.
I think this study is an interesting analysis,
but it is not terribly surprising. It seems
reasonable to think that patients who are
able to stay on treatment and get more
therapy will do better than those patients
who are not able to continue treatment.
Figure 2 is interesting. This is an analy-
sis of patients who received at least five
cycles of docetaxel and didn’t progress
stratified by number of cycles of chemo-
therapy. This tells us that, if you have
a patient who receives only 7 cycles of
docetaxel, he has a median survival of less
than 2 years, whereas if your patient gets
10 or more cycles, his median survival
is closer to 3 years. This gives us some
ability to predict how our patients will do
from a large and relatively contemporary
trial. And this prediction comes from the
number of cycles of chemotherapy that
the patient was able to receive.
Dr Lewis is Assistant
Professor of Clinical
Medicine in the Department
of Hematology and Medical
Oncology at Tulane
University School of
Medicine in New Orleans.
PROSTATE
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VOL. 2 • NO. 2 • 2017