Palliative chemotherapy for patients with breast cancer

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www.thelancet.com/oncology Vol 16 November 2015
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2 Ravandi F, O’Brien S, Thomas D, et al. First report of phase II study of
dasatinib with hyper-CVAD for the frontline treatment of patients with
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intensity chemotherapy combined with imatinib in adults with Ph-positive
acute lymphoblastic leukemia. Blood 2015; 125: 3711–19.
8 O’Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of
targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer 2012;
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Palliative chemotherapy for patients with breast cancer
In recent years, the survival of women with metastatic
breast cancer has improved substantially thanks to
advances in both cancer-specifi c management and
supportive care.1 As a result of prolonged survival
and the availability of many and better-tolerated
drugs, most women with metastatic breast cancer
will be eligible for several lines of chemotherapy.2
Indeed, clinicians in the USA reported in a survey that
they recommend an average of four to six lines of
chemotherapy for their patients with metastatic breast
cancer.3 Some women, particularly those with hormone-
receptor-positive or HER2-positive tumours, can have
eight or more chemotherapy regimens, because the
availability of several eff ective treatments and the
intrinsic natural history of the tumour enable several
lines of therapy.
The goal of treatment of metastatic breast cancer is to
prolong survival and improve quality of life by reducing
cancer-related symptoms. However, for the patient
who has been previously exposed to chemotherapy
(either in the context of adjuvant or metastatic setting),
there is no optimal sequence of administration of
chemotherapy drugs. This results in therapeutic choices
being made on the basis of extrapolations and the
physician’s previous experience. Although we all agree
that no single strategy can be used for all women, better
treatment strategies are pressingly needed.
Etirinotecan pegol is a long-acting topoisomerase I
inhibitor with high molecular weight, which restricts
its ability to cross intact vasculature into healthy
tissues, but promotes extravasation through leaky
tumour vessels. In a randomised phase 2 study, an
objective response of 29% was achieved among
patients with metastatic breast cancer who were
heavily pretreated.4 In The Lancet Oncology, Edith A
Perez and colleagues5 present BEACON, a phase 3
study designed to compare etirinotecan pegol with
physician’s choice (eribulin, vinorelbine, gemcitabine,
taxane, or ixabepilone) for women with previously
treated advanced breast cancer.
Unfortunately, the study did not demonstrate that
the new drug was better than existing treatments.
Although median overall survival was longer with
etirinotecan pegol than with treatment of physician’s
choice, this was not statistically signifi cant (hazard
ratio [HR] 0·87 [95% CI 0·75–1·02]; p=0·084). While the
authors deserve credit for selecting overall survival as
the study’s primary endpoint, the diff erence in median
overall survival between groups is not a meaningful
incremental gain.6 However, potential benefi ts were
noted in some subgroups; for instance, in a prespecifi ed
subset of 67 patients with brain metastases (8% of
patients at baseline; HR 0·51 [95% CI 0·30–0·86]), and
in the subgroup of 456 patients with liver metastases
(HR 0·73 [95% CI 0·59–0·89]). Etirinotecan pegol was
better tolerated compared with physicians’ therapeutic
choices, and relatively few grade 3 or higher toxicities
were reported. Quality of life was better-preserved
with etirinotecan pegol, though it declined during
chemotherapy in both groups.
CNS metastases constitute diffi cult clinical problems
and are the main cause of death in patients who have
experienced a relapse in the brain.7 Treatment options
include surgical excision of solitary metastases,
stereotactic radiosurgery for small (<3 cm) lesions, and
whole brain irradiation. Median survival for patients
Published Online
October 16, 2015
http://dx.doi.org/10.1016/
S1470-2045(15)00399-X
See Articles page 1556
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Comment
1454
www.thelancet.com/oncology Vol 16 November 2015
with CNS metastases is 4–6 months, and only 20–40%
of patients survive the fi rst year.7 In the past few years,
there has been increasing interest in assessment of
novel therapies for the treatment of breast cancer
that has metastasised to the brain, including local
and systemic approaches. At present, no cytotoxic or
targeted drugs have gained regulatory approval for
the treatment or prevention of breast cancer brain
metastases.8
Biomarker analyses are ongoing in the BEACON
study; however, the most predictive one could be as
simple as a brain CT suggestive of metastasis. In the
era of precision medicine, it is perhaps time to design
trials to compare standards of care in radiotherapy
against chemotherapy or targeted treatments and
to try to optimise our approach for palliation of
symptoms of breast cancer brain metastases. The
incidence of cognitive dysfunction in women receiving
brain radiotherapy has been shown to be substantial,
and one clinical advantage of chemotherapy in this
population might be to avoid this very disturbing
adverse event.9 In view of the improvements in
systemic therapies that led to longer overall survival,
we believe that development of both therapeutic and
preventive approaches for brain metastases are more
important now than ever before.
Emmanouil Saloustros, *Vassilis Georgoulias
General Hospital of Heraklion ‘Venizelio’, Heraklion, Greece (ES); and
Hellenic Oncology Research Group, 11471, Athens, Greece (ES, VG)
georgoul@med.uoc.gr
We declare no competing interests.
1 Chia SK, Speers CH, D’Yachkova Y, et al. The impact of new
chemotherapeutic and hormone agents on survival in a population-based
cohort of women with metastatic breast cancer. Cancer 2007; 110: 973–79.
2 Cardoso F , Di LA, Lohrisch C, Bernard C, Ferreira F, Piccart MJ. Second and
subsequent lines of chemotherapy for metastatic breast cancer: what did
we learn in the last two decades? Ann Oncol 2002; 13: 197–207.
3 Seah DS, Luis IV, Macrae E, et al. Use and duration of chemotherapy in
patients with metastatic breast cancer according to tumor subtype and line
of therapy. J Natl Compr Canc Netw 2014; 12: 71–80.
4 Awada A, Garcia AA, Chan S, et al. Two schedules of etirinotecan pegol
(NKTR-102) in patients with previously treated metastatic breast cancer:
a randomised phase 2 study. Lancet Oncol 2013; 14: 1216–25.
5 Perez EA, Awada A, O’Shaughnessy J, et al. Etirinotecan pegol (NKTR-102)
versus treatment of physician’s choice in women with advanced breast
cancer previously treated with an anthracycline, a taxane, and capecitabine
(BEACON): a randomised, open-label, multicentre, phase 3 trial.
Lancet Oncol 2015; published online Oct 16. http://dx.doi.org/10.1016/
S1470-2045(15)00332-0.
6 Sheik-You souf A, Gandhi S, Dukhovny S, Verma S. A comparison of
physician and patient perceptions of clinically important endpoints in the
treatment of Metastatic Breast Cancer (MBC). EJC Supplements 2010; 8: 77.
7 Pestalozz i BC, Francis P, Quinaux E, et al. Is risk of central nervous system
(CNS) relapse related to adjuvant taxane treatment in node-positive breast
cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98
Trial. Annal Oncol 2008; 19: 1837–41.
8 Lin NU, A miri-Kordestani L, Palmieri D, Liewehr DJ, Steeg PS.
CNS metastases in breast cancer: old challenge, new frontiers.
Clin Cancer Res 2013; 19: 6404–18.
9 Brown P, Asher A, Ballman K, Farace E, Cerhan J, Anderson S. NCCTG N0574
(Alliance): a phase III randomized trial of whole brain radiation therapy
(WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain
metastases. Proc Am Soc Clin Oncol 2015; 33: Abstr LBA4.
Morcellation of uterine leiomyomas: a plea for patient triage
Uterine leiomyomas are the most common tumours of
the genital tract; nearly 70% of white women and more
than 80% of black women will have at least one by the
age of 50 years. Treatment is necessary in 15–30% of
these women.1 Apart from this benign lesion, the uterus
can harbour malignant tumours, including endometrial
cancer and tumours of mesenchymal origin, so-called
sarcomas. These include a wide range of monophasic
or biphasic tumours, including leiomyosarcoma,
endometrial stromal sarcoma, smooth-muscle tumour of
uncertain malignant potential, undiff erentiated sarcoma,
adenosarcoma, and some very rare tumours. Between
1970 and 2000, 419 uterine sarcomas were registered
in Norway.2 Based on NOCCA and NORDCAN databases,
incidence rates were about 0·3 cases per 100 000 for
endometrial stromal sarcoma and about 0·4 cases per
100 000 for leiomyosarcoma.3
The diff erentiation of benign and malignant lesions
requires expert pathologists. It is therefore not
surprising that imaging frequently fails to identify
malignant mesenchymal uterine tumours.4,5 CT scans
inform little about uterine details and have generally
been used to identify extrauterine extension in the
pelvis and metastatic disease. On MRI, the appearance
of leiomyosarcoma is variable and pathognomic
features of malignancy are lacking, especially for small
tumours.5
Morcellation is part of the endoscopic
armamentarium and is designed to remove large
leiomyomas, thus avoiding laparotomy and its
associated longer recovery period and possible
complications. However, morcellation and spilling
of malignant cells changes the natural spread
pattern and increases the risk of transperitoneal