News

A vaccine developed for breast cancer

has been shown to be safe and might
help to slow the cancers progression,
according to phase 1 trial ndings.
Mammaglobin-A (MAM-A) is a
secretary protein expressed almost
exclusively in breast cancer and overexpressed in up to 80% of primary
metastatic breast cancers. This
makes the protein a prime candidate
for breast cancer vaccine therapy.
For this study, William Gillanders
and
colleagues
vaccinated
14 patients who had metastatic
breast cancer that expressed MAM-A
with three doses of a 4 mg MAM-A
DNA vaccine to assess the vaccines
safety.
Overall, the vaccine was safe,
with only grade 12 adverse events,
such as vaccine site tenderness
and
mild
u-like
symptoms
reported by the patients. The

frequency of MAM-A-specic CD8

T cells signicantly increased after
vaccination (09% [SD 05%] vs 38%
[SD 12%]; p<0001), and investigators
recorded signicant responses in
six patients.
MAM-A vaccination was associated
with prolonged progression-free
survival (6 month PFS 53% vs 33%;
p=0011); although the study was not
powered to formally assess survival.
Of the 14 patients who received
the vaccine, about half showed no
progression of their cancer 1 year
after receiving the vaccine. In a
control group of 12 patients who
were not vaccinated, only one-fth
showed no cancer progression after
1 year.
Lead researcher William Gillanders
(Washington University School of
Medicine, Saint Louis, MO, USA), said:
The study conrms that MAM-A

is an attractive target for a breast

cancer vaccine, especially given the
specicity of tissue expression of
MAM-A. The next step is to test the
MAM-A DNA vaccine in patients with
newly diagnosed breast cancer being
treated with neoadjuvant endocrine
therapy.
Sally Greenbrook, of Breakthrough
Breast Cancer (London, UK), added:
These are very interesting results,
and this work could eventually lead
to a therapeutic treatment or a
vaccine that could be used in breast
cancer prevention. However, she
also cautions that it is important to
remember that this was a very smallscale trial designed to see whether
the treatment is safe and eective, so
any vaccine against breast cancer is
likely still some years away.

Stanley Flegler/Science Photo Library

Breast cancer vaccine shows promise

Published Online
December 5, 2014
http://dx.doi.org/10.1016/
S1470-2045(14)71166-0
For the study by Gillanders and
colleagues see Clin Cancer Res
2014; 20: 5964

Sanjay Tanday

Anti-PD-L1 antibody active in metastatic bladder cancer

Findings of a phase 1 study of
the immune checkpoint inhibitor
MPDL3280A have shown rapid and
ongoing responses in patients with
metastatic urothelial bladder cancer.
MPDL3280A, an antibody that targets
the programmed death ligand 1
(PD-L1), which is expressed on activated
T cells. A high proportion of patients
whose tumours expressed PD-L1-positive tumour-inltrating immune cells
acheived an overall response. The safety
prole of MPDL3280A immunotherapy
showed low toxicity, including a lack of
renal toxicity, suggesting the treatment
might be better tolerated in elderly
patients who are less able to tolerate
chemotherapy. 57% of patients had
a treatment-related adverse event,
of which three events were grade 3
(asthenia, thrombocytopaenia, and
decreased blood phosphorus).
Patients in the study received
the drug for a median of 65 days
(range 1259 days) and 67 patients
www.thelancet.com/oncology Vol 16 January 2015

were assessed for treatment ecacy,

17 (25%) of whom showed a response.
After at least 6 weeks of follow-up,
13 (43%) of 30 patients with tumours
with high PD-L1 expression achieved
objective responses (95% CI 2663),
and 7% of these patients showed
complete responses; only 4 (11%) of
35 patients with tumours with lower
levels of PD-L1 expression achieved an
objective response (426).
After at least 12 weeks of follow-up,
13 (52%) of 25 patients achieved an
objective response (95% CI 3270%).
16 of the 17 responders had ongoing
responses, and all continued on
treatment. For patients with high
PD-L1 expression, the duration
of response ranged from 01 to
303 weeks, and for those with lower
expression from 01 to 60 weeks.
This treatment appears active
in individuals with advanced
bladder cancer, who have no other
treatment available to them, said

lead investigator Thomas Powles

(Barts Cancer Institute, University of
London, London, UK). Bladder cancer
has a high rate of somatic and driver
mutations, which appear to inuence
ecacy, Powles added.
These results are spectacular,
said Padmanee Sharma, University
of Texas MD Anderson Cancer Center
(Houston, TX, USA). There have been
no second-line treatments available
to patients with advanced bladder
cancer, and no new treatments for
30 years, she said.
The study initially included only
patients whose tumour-inltrating
cells showed high PD-L1 expression,
but was later expanded to include
others
irrespective
of
PD-L1
expression. The drug is now being
tested in large, randomised phase 2
trials, and will begin phase 3 testing
within a month, Powles said.

Published Online
December 5, 2014
http://dx.doi.org/10.1016/
S1470-2045(14)71167-2
For the study by Powles and
colleagues see Nature 2014;
515: 55862

Vicki Brower
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