Correspondence

I declare that I have no conicts of interest.

Carsten Nieder
carsten.nieder@nlsh.no
Department of Oncology and Palliative Medicine,
Nordland Hospital, Bod, and Institute of Clinical
Medicine, Faculty of Health Sciences, University of
Troms, Troms, Norway
1

Bachelot T, Romieu G, Campone M, et al.

Lapatinib plus capecitabine in patients with
previously untreated brain metastases from
HER2-positive metastatic breast cancer
(LANDSCAPE): a single-group phase 2 study.
Lancet Oncol 2013; 14: 6471.
Lin NU, Eierman W, Greil R, et al.
Randomized phase II study of lapatinib plus
capecitabine or lapatinib plus topotecan for
patients with HER2-positive breast cancer
brain metastases. J Neurooncol 2011;
105: 61320.
Lin NU, Carey LA, Liu MC, et al. Phase II trial of
lapatinib for brain metastases in patients with
human epidermal growth factor receptor
2-positive breast cancer. J Clin Oncol 2008;
26: 199399.
Li J, Bentzen SM, Renschler M, Mehta MP.
Regression after whole-brain radiation
therapy for brain metastases correlates with
survival and improved neurocognitive
function. J Clin Oncol 2007; 25: 126066.
Kased N, Binder DK, McDermott MW, et al.
Gamma Knife radiosurgery for brain
metastases from primary breast cancer.
Int J Radiat Oncol Biol Phys 2009; 75: 113240.
Xu Z, Marko NF, Chao ST, et al. Relationship
between HER2 status and prognosis in
women with brain metastases from breast
cancer. Int J Radiat Oncol Biol Phys 2012;
82: e73947.

Thomas Bachelot and colleagues

describe the use of lapatinib plus
capecitabine for the treatment of
HER2-positive metastatic breast
cancer with brain metastases, in
patients not previously treated with
either of whole-brain radiotherapy
(WBRT), laptanib, or capecitabine.1
Of the 44 patients who were
assessed after treatment with lapatinib
plus capecitabine, only 29 had partial
responses, with no patient achieving a
complete response. Toxicity rates were
high, with almost a third of patients
having at least one severe adverse
event, and 9% of patients having to
stop treatment because of toxicity.
Also, 20% of patients experienced
palmar-plantar
erythrodysesthesia,
a condition which can have a severe
eect on quality of life. 2
The authors acknowledge that
quality of life and neurocognitive
www.thelancet.com/oncology Vol 14 January 2013

eects were not measured. The

authors also acknowledge that
they are unable to directly compare
the combination of lapatinib plus
capecitabine with WBRT, given the
study design. However, Bachelot
and colleagues state1 that they are
planning a randomised trial to test
whether upfront systemic therapy
with lapatinib and capecitabine
is better than WBRT in previously
untreated brain metastases from
HER2-positive breast cancer.
Patients with brain metastases have
a tendency for quick deterioration
in the absence of eective therapy.
Although WBRT might oer a
short treatment course with a
good probability of disease control,
lapatinib and capecitabine involves
the daily consumption of two drugs
which are known to cause diarrhoea,
dermatitis, and fatigue, all of which
can worsen quality of life.3,4 Bachelot
and colleagues concern regarding
cognitive decline after WBRT could
be unfounded, given that cognitive
decline is a late toxicity that might or
might not occur even if the patient
survived for many years.
We believe that, rather than
comparing upfront treatment with
WBRT with lapatinib and capecitabine,
a more rational approach would be
to develop strategies that explore
the potential benets of integrating
WBRT with chemotherapy. Another
attractive area of investigation would
be to combine the use of stereotactic
radiosurgery against brain metastases
while using lapatinib and capecitabine
against coexisting systemic metastatic
disease, given that the combination
of radiosurgery with WBRT has been
shown to improve not only the
response rates, but also the duration
of response.5
We declare that we have no conicts of interest.

Sridhar Papaiah Susheela,

*Swaroop Revannasiddaiah,
N Madhusudhan,
Ajaikumar Basavalingaiah
swarooptheone@gmail.com

Department of Radiation Oncology, HealthCare

Global, Bangalore Institute of Oncology, 2nd Cross,
Raja Rammohan Roy Extension, Bengaluru 560027,
India
1

3
4

Bachelot T, Romieu G, Campone M, et al.

Lapatinib plus capecitabine in patients with
previously untreated brain metastases from
HER2-positive metastatic breast cancer
(LANDSCAPE): a single-group phase 2 study.
Lancet Oncol 2013; 14: 6471.
Webster-Gandy JD, How C, Harrold K.
Palmar-plantar erythrodysesthesia (PPE): a
literature review with commentary on
experience in a cancer centre. Eur J Oncol Nurs
2007; 11: 23846.
Walko CM, Lindley C. Capecitabine: a review.
Clin Ther 2005; 27: 2344.
Moy B, Goss PE. Lapatinib-associated toxicity
and practical management recommendations.
Oncologist 2007; 12: 75665.
Kondziolka D, Patel A, Lunsford LD, Kassam A,
Flickinger JC. Stereotactic radiosurgery plus
whole brain radiotherapy versus radiotherapy
alone for patients with multiple brain
metastases. Int J Radiat Oncol Biol Phys 1999;
45: 42734.

Authors reply
We thank Carsten Nieder and Sridhar
Susheela and colleagues for their
thoughtful comments on our study
of frontline chemotherapy for brain
metastases in patients with HER2positive metastatic breast cancer.1
Nieder and Susheela rightly point
out some of the weakness of our
trial, mainly the absence of data
regarding neurocognitive function
and quality of life. We also could
not assess whether a strategy of
frontline chemotherapy followed
by radiotherapy at progression will
result in greater benet for the
patient than an alternative approach,
with cerebral radiotherapy before
or directly after chemotherapy. We
agree that this question is important,
but it could not be answered by a
study such as LANDSCAPE, which
was a phase 2 non-randomised trial
with response rate as the primary
endpoint.1
Nieder mentions the possibility
that a large proportion of our
patients might have been treated
with stereotactic radiosurgery and
that this treatment could have
led to better disease control and
survival. We agree that radiosurgery
is a valid treatment option for
e3