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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.
Atezolizumab as first-line in cisplatin-ineligible patients with
advanced urothelial carcinoma
C
isplatin-based chemotherapy has
been the mainstay in the treatment
of metastatic urothelial cancer.
Unfortunately, over 60% of patients are
ineligible to receive this treatment. Reasons
include poor performance status, impaired
renal function or heart failure.
Atezolizumab, a class of checkpoint inhibitor
immunotherapy, targets the protein PD-L1
found on tumour cells. PD-L1 binding to
PD-1 on immune cells supresses the host
immune response.
Balar and colleagues report the promising
results of a multicentre, non-randomised
single-arm, phase 2 study of atezolizumab in
a cohort of patients with locally advanced or
metastatic urothelial carcinoma not suitable
for cisplatin-based chemotherapy. For the 119
patients who received one or more doses of
atezolizumab, the overall response rate was
23%; complete response rate was 9% and
70% of responses were on-going. Median
overall survival was 15.9 months. Treatment
related adverse events included fatigue (30%),
diarrhoea (12%), and pruritis (8%). There
was one treatment-associated mortality due
to sepsis, and treatment was discontinued
in 8%. Reassuringly, nephrotoxicity has been
reportedly low in this cohort.
This is a critical study; it reveals similar
response rates to previous studies involving
checkpoint inhibitors. Immunotherapy
appears to be much easier to tolerate
than chemotherapy, and this is especially
important for elderly patients or those with
significant renal impairment.
However, with less than 30% of patients
responding to the drug, future studies
are essential in the predictive biomarkers
field to determine response. The future
also necessitates studies evaluating drug
sequencing, combination therapy with
chemotherapy, PD-1 inhibitors (eg,
pembrolizumab), and the role of neoadjuvant
therapy in muscle invasive disease. We
remain at the tip of a very exciting iceberg.
Atezolizumab for advanced
urothelial carcinoma, adjuvant
sunitinib for high-risk RCC after
nephrectomy and 10-year outcomes
for localised prostate cancer
Drs Rajesh Nair and Homi Sagar share
their top three recent clinical trials –
S-TRAC, ProtecT and IMvigor210 – and
their impact on patients with bladder,
renal and prostate cancers.
Atezolizumab as first-line treatment in cisplatin-ineligible
patients with locally advanced and metastatic urothelial
carcinoma: a single-arm, multicentre, phase 2 trial.
Lancet
2016 Dec 7; [Epub ahead of print]. AV Balar, MD Galsky, JE Rosenberg, et al; IMvigor210
Study Group.
Take-home message
•
This was a multicentre, single-arm, phase 2 study evaluating the safety and efficacy of first-
line atezolizumab monotherapy (1200 mg fixed dose) in 123 cisplatin-ineligible patients with
advanced urothelial carcinoma. The objective response rate was 23%. Tumour mutation
load was associated with response. Median overall survival was 15.9 months.
•
Results indicated that atezolizumab is active in patients with advanced, untreated cisplatin-
ineligible urothelial carcinoma.
EDITOR’S PICKS
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