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Low to modest reductions in neutropenia-related hospitalisations
observed with colony-stimulating factors
Comment by
Lee Schwartzberg,
MD, FACP
G
rowth factor support with
granulocyte-colony stimulat-
ing factor (G-CSF) reduces
the incidence of febrile neutropenia,
hospitalisation, and death in patients
at high risk of myelosuppression
from chemotherapy, which is com-
monly considered at a threshold lev-
el of >20% risk without prophylaxis.
But, which patients receiving inter-
mediate-risk regimens, with a 10%
to 20% risk of febrile neutropenia,
deserve G-CSF prophylaxis and
what are the clinical and economic
benefits of the intervention? This
retrospective claims-based study
adds an important analysis of
use of growth factor in the breast
cancer setting with three common
regimens: TC, TCH, and non-dose
dense AC. The investigators found
that the TC and TCH regimens plus
G-CSF, overwhelmingly adminis-
tered as long-acting pegfilgrastim,
were associated with a reduction in
hospitalisation. In contrast, women
taking AC, a regimen considered
low risk by guidelines, did not derive
benefit from growth factor.
In the TC/TCH groups, the re-
duction in hospitalisation benefit
was pronounced in older patients
(>65 years of age) who received
prophylaxis. This finding is very
much in keeping with guidelines,
which suggest, for intermediate-risk
regimens, that patient risk factors
are very important to consider. Risk
factors include age, comorbidi-
ties, prior history of neutropenia,
and prior chemotherapy. While for
the overall group analysed in this
study the strict cost–benefit ratio
was modest, the clinician who ap-
plies the principles of judiciously
using growth factor support with
moderate-risk regimens will reduce
the adverse events associated with
chemotherapy in breast cancer and
likely do so in a cost-effective, re-
sponsible manner.
Dr Schwartzberg
is Senior Partner
and Medical
Director, The
West Clinic,
Memphis,
Tennessee.
Dual block with lapatinib and trastuzumab effective as
neoadjuvant treatment of HER2-postive breast cancer
Comment by Lee Schwartzberg,
MD, FACP
A
ddition of lapatinib, a small-molecule
HER2 inhibitor, to trastuzumab with
chemotherapy led to improvement
in the pathologic complete response rate in
the neoadjuvant setting but not disease-free
survival benefit in the adjuvant setting. This
meta-analysis teases out the relative benefit of
lapatinib, and finds that its biggest impact is in
the ER− subgroup and those patients receiving
single-agent taxane. In an era when combina-
tion chemotherapy is typically delivered with
anti-HER2 agents, the incremental benefit of
lapatinib is small and nonsignificant. However,
given the growing use of single-agent taxane
plus trastuzumab in lower-risk patients or
patients with more comorbidities, one can
conjecture a setting in which adding lapatinib
instead of more cytotoxic chemotherapy would
make sense in the neoadjuvant/adjuvant set-
ting. It would be interesting to see a prospec-
tive trial test this idea.
HER2 biosimilars in clinical practice: an interviewwith
Dr William Gradishar
INTERVIEW WITH WILLIAM GRADISHAR, MD, FACP
Dr Gradishar discusses the Heritage trial on the
trastuzumab biomimilar for HER2+ metastatic
breast cancer and shares his thoughts on using
biosimilars in practice. Dr Gradishar is Betsy Bram-
sen Professor of Breast Oncology
in the Division of Hematology and
Medical Oncology, Department of
Medicine, at the Feinberg School
Medicine at Northwestern Univer-
sity in Chicago, Illinois.
Advances in genomic testing and computational
biology for breast cancer
INTERVIEW WITH KIMBERLY BLACKWELL, MD
Dr Blackwell discusses the latest advances in
genomic testing and gene expression profiles, in-
cluding results of the MINDACT trial and immune
checkpoint inhibitors. Dr Blackwell
is Professor of Medicine and Assis-
tant Professor in Radiation Oncol-
ogy, Duke Department of Medicine,
North Carolina.
Risk of neutropenia-related hospitalization in patients who received
colony-stimulating factors with chemotherapy for breast cancer
Journal of Clinical Oncology
Take-home message
•
The authors evaluated 4815 patients with breast cancer who received docetaxel and cyclophosphamide
(TC), docetaxel, carboplatin, and trastuzumab (TCH), and doxorubicin and cyclophosphamide (AC) to
determine if granulocyte–colony stimulating factor (G-CSF) prophylaxis improved neutropenia-related
hospitalizations. Results showed that G-CSF given within 5 days of starting chemotherapy was associated
with reduced risk of neutropenia-related hospitalization in patients taking TC (adjusted OR, 0.29) and
in those taking THC (adjusted OR, 0.19) but not in those taking AC (adjusted OR, 1.21).
•
There was a low to modest benefit relative to neutropenia-related hospitalizations associated with
G-CSF prophylaxis in breast cancer patients being treated with TC and TCH.
Abstract
PURPOSE
To describe outcomes after granulocyte
colony-stimulating factor (G-CSF) prophylaxis in pa-
tients with breast cancer who received chemotherapy
regimens with low-to-intermediate risk of induction of
neutropenia-related hospitalization.
PATIENTS AND METHODS
We identified 8,745 patients
age ≥ 18 years from a medical and pharmacy claims
database for 14 commercial US health plans. This
retrospective analysis included patients with breast
cancer who began first-cycle chemotherapy from 2008
to 2013 using docetaxel and cyclophosphamide (TC);
docetaxel, carboplatin, and trastuzumab (TCH); or doxo-
rubicin and cyclophosphamide (conventional-dose
AC) regimens. Primary prophylaxis (PP) was defined
as G-CSF administration within 5 days of beginning
chemotherapy. Outcome was neutropenia, fever,
or infection-related hospitalization within 21 days of
initiating chemotherapy. Multivariable regressions and
number-needed-to-treat analyses were used.
RESULTS
A total of 4,815 patients received TC (2,849 PP;
1,966 no PP); 2,292 patients received TCH (1,444 PP;
848 no PP); and 1,638 patients received AC (857 PP;
781 no PP) regimen. PP was associated with reduced
risk of neutropenia-related hospitalization for TC (2.0%
PP; 7.1% no PP; adjusted odds ratio [AOR], 0.29; 95% CI,
0.22 to 0.39) and TCH (1.3% PP; 7.1% no PP; AOR, 0.19;
95% CI, 0.12 to 0.30), but not AC (4.7% PP; 3.8% no PP;
AOR, 1.21; 95% CI, 0.75 to 1.93) regimens. For the TC
regimen, 20 patients (95% CI, 16 to 26) would have to
be treated for 21 days to avoid one neutropenia-related
hospitalization; with the TCH regimen, 18 patients (95%
CI, 13 to 25) would have to be treated.
CONCLUSION
Primary G-CSF prophylaxis was associated
with low-to-modest benefit in lowering neutropenia-
related hospitalization in patients with breast cancer
who received TC and TCH regimens. Further evaluation
is needed to better understand which patients benefit
most from G-CSF prophylaxis in this setting.
J Clin Oncol
2016 Sep 19;[Epub ahead of print], Agiro
A, Ma Q, Acheson AK, et al.
Dual block with lapatinib and trastuzumab vs single-agent
trastuzumab combined with chemotherapy as neoadjuvant
treatment of HER2-positive breast cancer: a meta-analysis of
randomized trials
Clinical Cancer Research
Take-home message
•
This meta-analysis assessed neoadjuvant combination of lapa-
tinib and trastuzumab vs trastuzumab alone in HER2-positive
breast cancer. The combination was associated with a 13%
absolute improvement in pathologic complete response com-
pared with trastuzumab alone (summary risk difference, 0.13).
Interestingly, in hormone receptor-negative patients, there
was greater activity with trastuzumab alone compared with
the hormone receptor-positive or hormone receptor-negative
patients treated with the dual block.
•
The authors conclude that patients with HER2-positive breast
cancer benefit from the neoadjuvant combination of lapatinib
and trastuzumab, while hormone receptor–negative patients
demonstrate the best results with taxane monotherapy.
Abstract
PURPOSE
(Neo)adjuvant treat-
ment with chemotherapy plus
trastuzumab reduces recurrence
and death risk in HER2-positive
(HER2+) breast cancer. Rand-
omized trials assessed HER2
dual block by adding lapatinib to
trastuzumab and chemotherapy
in the neoadjuvant setting using
pathologic complete response
(pCR) as the outcome measure.
We conducted a meta-analysis of
randomized trials testing neoadju-
vant dual block with lapatinib and
trastuzumab versus trastuzumab
alone in HER2+ breast cancer.
EXPERIMENTAL DESIGN
Trials were
identified by Medline (PubMed),
ISI Web of Science (Science Cita-
tion Index Expanded), Embase,
Cochrane library, and reference
lists of published studies, review
articles, editorials, and by hand-
searched reports from major
cancer meeting reports.
RESULTS
Six randomized trials
including 1,155 patients were
identified, of whom 483 (41.8%)
were hormone receptor-negative,
672 (58.2%) hormone receptor-
positive, 534 (46.2%) received
taxanes alone, and 621 (53.8%)
anthracyclines plus taxanes or
the docetaxel-carboplatin regi-
men. Overall, the dual block was
associated with a significant 13%
absolute improvement in pCR rate
compared with single-agent tras-
tuzumab (summary risk difference,
SRD 0.13; 95% CI, 0.08–0.19). The
activity was greater in hormone
receptor-negative patients who
received chemotherapy with
taxanes alone (SRD 0.25; 95%
CI, 0.13–0.37), compared to hor-
mone receptor-positive or hor-
mone receptor-negative disease
treated with anthracyclines plus
taxanes or the docetaxel-carbo-
platin regimen (SRD 0.09; 95%
CI, 0.02–0.15; Pinteraction = 0.05).
CONCLUSIONS
On the basis of
ΔpCR data, the dual block with
trastuzumab and lapatinib plus
chemotherapy is a very active
treatment only in HER2(+) and
hormone receptor-negative
breast cancer treated with taxane
monochemotherapy.
Clin Cancer Res
2016;22:4594-
4603, Clavarezza M, Puntoni M,
Gennari A, et al.
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