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Rajesh Nair, FRCS (Urol), FEBU, MSc is a
UK-trained urological surgeon undergoing
advanced fellowship training in robotics and uro-
oncology at the Royal Melbourne Hospital.
Homayoun (Homi) Zargar, MD, FRACS is a
urological surgeon with fellowship training in uro-
oncology, and advanced laparoscopic and robotic
surgery. He is Consultant Urologist at the Royal
Melbourne Hospital and Senior Clinical Lecturer,
Department of Surgery, University of Melbourne.
Nivolumab in metastatic urothelial carcinoma after platinum
therapy (CheckMate 275)
T
raditional treatment for metastatic
bladder cancer is cisplatin-based
chemotherapy. Unfortunately, due
to comorbidities, deteriorating renal func-
tion or cardiac impairment, over 60% of
patients are ineligible to receive this treat-
ment. Their prognosis is poor.
Nivolumab, is a humanised IgG4 PD-1
immune checkpoint inhibitor. This form of
immunotherapy targets the protein PD-L1
found on tumour cells binding to PD-1 on
immune cells suppressing the host immune
response.
Sharma et al report the promising results
of a multicentre, phase II, single-arm study
examining nivolumab in patients with
metastatic or locally advanced urothelial
carcinoma, whose disease progressed or
recurred despite previous platinum-based
chemotherapy. Patients received nivolumab
3 mg/kg intravenously every 2 weeks until
disease progression, clinical deteriora-
tion or as a result of toxicity. Of the 265
patients evaluated, median follow-up was 7
months, with an overall objective response
rate of 19.6%. Interestingly, this study
goes one step further. PD-L1 expression
was recorded from tissue obtained (>5%
and 1%). Of those who expressed >5% and
>1% PD-L1 expression, response to nivoul-
mab was 28.4% and 23.8%, respectively.
Nivolumab in metastatic urothelial carcinoma after platinum therapy
(CheckMate 275): a multicentre, single-arm, phase 2 trial
Lancet Oncol
2017 Jan 25;[EPub Ahead of Print], P Sharma, M Retz, A Siefker-Radtke, et al
Take-home message
•
In this single-arm study, 265 patients with metastatic or surgically unresectable
advanced urothelial carcinoma were given nivolumab, a PD-1 inhibitor. A confirmed
objective response was achieved in 28.4% (23/81), 23.8% (29/122), and 16.1%
(23/143) of patients with PD-L1 expression
≥
5%,
≥
1%, and <1%, respectively. Overall
survival was 7 months.
•
Nivolumab treatment has an acceptable safety profile and is clinically beneficial,
but improved outcomes did not correlate with PD-L1 expression in patients with
unresectable advanced urothelial carcinoma.
Higher rates of long-term overall survival with radiation and
antiandrogen therapy for recurrent prostate cancer
T
raditional standard of care for patients
who exhibit biochemical recurrence
(elevated and rising prostate-spe-
cific antigen [PSA] level) and therefore
recurrent prostate cancer following radical
prostatectomy is salvage radiotherapy. Shi-
pley and colleagues evaluate the impact of
adding an antiandrogen on disease-specific
and overall survival. This double-blind pla-
cebo controlled study assessed 760 men
who had undergone radical prostatectomy
with pelvic lymphadenectomy with patho-
logical T-stage, T2 or T3 and N0 prostate
adenocarcinoma. All patients demonstrated
evidence of biochemical recurrence as
defined by a PSA of 0.2–4.0 ng/mL and
were randomised to salvage radiation
therapy alone or in combination with bical-
utamide monotherapy (150 mg/day) for 2
years.
With a median follow-up of 13 years, over-
all survival at 12 years was 76.3% in the
bicalutamide group vs 71.3% in the pla-
cebo group. Death from prostate cancer was
5.8% vs 13.4% in the bicalutamide and pla-
cebo groups, respectively. Finally incidence
of metastatic disease at 12 years was 14.5%
and 23% in the bicalutamide and metastatic
disease groups, respectively.
This study is unique in demonstrating the
addition of antiandrogen therapy to sal-
vage radiation therapy reduced overall and
cancer-specific survival, and progression
to metastatic disease. However, there are
a number of caveats one must consider
when evaluating the data presented. Most
concomitant androgen deprivation regi-
mens focus on using a luteinising hormone
releasing hormone analogue. Certainly, most
comparative ongoing salvage radiation trials
use this and not bicalutamide, which here
is delivered at the 150 mg once daily. This
is far higher than the recommended dosage
of 50 mg once daily. In addition, the timing
of adjuvant radiation in this cohort of trial
patients appears to be significantly delayed
when compared to the current standard,
which is when PSA reaches 0.2–0.5 ng/dL.
Certainly, this patient cohort is an impor-
tant one for urologists and oncologists alike.
While this study certainly is informative, we
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