2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

available data comes from an era when taxane adjuvant use
was not yet standard, and even anthracycline-based regimens
were not always used. These data may not apply to our
current MBC patient population.
Available trials have produced the following conclusions:
for taxane-naive and anthracycline-naive/minimally exposed
patients, single-agent anthracycline or single-agent
taxane yield similar results; for taxane-naive and anthracycline-resistant/refractory
patients, single-agent taxane led
to better outcomes than single-agent anthracyclines; combinations
of anthracyclines plus taxanes in the metastatic
setting consistently led to higher response rates, sometimes
higher time to progression or PFS, higher toxicity, but not
better OS. Because of this, sequential single agent therapy
is not only appropriate, but preferred for most patients. A
2008 meta-analysis of individual patient data concludes that
taxanes do not improve survival when compared with anthracyclines,
either as single agents or in anthracycline
combinations and that taxanes in combination with anthracyclines
modestly improve response rate (RR) and PFS but
not OS. 13
For patients pretreated with both anthracyclines and
taxanes, the most consistent data concerns capecitabine use.
Vinorelbine has been compared head-to-head with docetaxel
and yielded similar efficacy and significantly less toxicity.
Given that both these agents are available as oral formulations
and are associated with much less toxicity including
alopecia, they are attractive options. Although there is also
some data supporting rechallenging with taxanes as firstline
therapy, the wealth of other available options and
toxicity concerns make this a less appealing option.
A common question relates to the use of combination of
cytotoxic agents compared with their sequential use as
monotherapy. Available evidence 14 suggests monotherapy
as the preferred option (even in the presence of visceral
metastases) in all cases except those with a rapid progressive
or highly symptomatic disease.
It is important to know that there are no data to support
an optimal sequence of therapies and that only eribulin led
to an OS benefit. Therefore, treatment decisions must be
individualized, taking into account many other factors beyond
efficacy.
Chemotherapy: Optimal Duration and Number of Lines of Therapy
Many studies have looked into the question of optimal
duration of systemic therapy, mainly chemotherapy, for
which the balance between efficacy and toxicity is perhaps
more difficult to achieve. Recently, a meta-analysis of published
trials 15 has looked into this issue and concluded that
longer first-line chemotherapy duration is associated with
marginally longer OS and a substantially longer PFS, and
treatment should be prescribed until progression or unacceptable
toxicity.
Treatment Present: Metastatic Breast Cancer in 2012
Today’s systemic treatment decisions are guided by a
range of factors: 1) the subtype of the breast cancer (defined
by ER status and HER2) 2) sites of disease 3) disease tempo
4) presence and extent of symptoms 5) prior therapy 6)
availability of effective local therapy and 7) patient preferences.
30
Hormone Receptor-Positive MBC
Hormone therapy is the preferred first-line treatment for
most. Several options are available, including the AIs
tamoxifen and fulvestrant (not U.S. Food and Drug Administration
(FDA)-approved for first-line use). In postmenopausal
patients who present de novo with metastatic disease
or those who have only received tamoxifen in the adjuvant
setting, treatment with an AI is standard of care. 16 A
substantial number of these patients remain on an AI with
disease control for prolonged periods. In a minimally symptomatic
patient without an extensive disease burden, it is
reasonable to try a second-line agent, even if there has been
no or little benefit with the initial treatment. Among patients
who develop disease progression after an objective
response or prolonged disease stabilization on first-line
treatment, another endocrine agent is generally preferred.
Treatment with fulvestrant, a steroidal AI (assuming a
nonsteroidal agent was used initially) or tamoxifen (unless
there had been prior progression on tamoxifen) are reasonable.
17 Unfortunately, clinical benefit from second-line therapy
in the metastatic setting is less impressive than with
first-line treatment. Some patients will continue to derive
benefit from hormone therapy and can go on to receive thirdand
fourth-line therapy.
Many patients with a new diagnosis of MBC will have
already progressed on an adjuvant aromatase inhibitor. For
these, options are more limited. In general, fulvestrant is
used as the first-line metastatic treatment in such patients.
A recent study conducted by the Southwest Oncology Group
that compared anastrozole alone with anastrozole plus fulvestrant
in the first-line setting 18 suggested an advantage
both in terms of PFS and OS for the combination.
In premenopausal women with MBC, tamoxifen remains
the standard treatment, often administered in conjunction
with a luteinizing hormone releasing hormone (LHRH) agonist.
19 For premenopausal women who develop metastatic
disease while on tamoxifen, the usual approach is a combination
of an LHRH agonist and an AI. AIs are ineffective in
women with functioning ovaries.
Ultimately, women with hormone receptor-positive disease
become refractory to endocrine therapy. At that point,
chemotherapy is administered. A wide variety of choices are
available, and treatment options are similar to those that
are available for women with triple-negative disease. Both
the taxanes and capecitabine are commonly given in the
first-line setting. Although capecitabine does not have FDA
approval for first-line therapy, several small studies comparing
capecitabine with other agents have suggested that
capecitabine is a reasonable initial approach. 20
Triple-Negative Breast Cancer
SLEDGE, CARDOSO, WINER, AND PICCART
Options are limited to chemotherapy in patients with
triple-negative breast cancer. Most patients have received
adjuvant chemotherapy, often with a short disease-free
interval. For these reasons, chemotherapy options in the
metastatic setting are often limited. Survival from the time
of metastatic disease tends to be relatively short, with a
median of approximately 1 year. 21
Treatment options for metastatic triple-negative disease
include all of the available chemotherapeutic agents and
regimens. Given the widespread use of anthracyclines in the
adjuvant setting, these agents are not commonly used in the