Transcript Breast Update - ASCO 2007

Highlights of Metastatic
Breast Cancer Research
ASCO 2007: Highlights of
Metastatic Breast Cancer Research
Single-Agent First-Line Therapy

New data show improved clinical activity of nab-paclitaxel compared
with docetaxel in patients with advanced breast cancer
Combination Therapy for First-Line Treatment
of Metastic Breast Cancer

First-line data for lapatinib in HER2-positive advanced breast cancer
is encouraging

Adding a platinum to a taxane plus trastuzumab does not add to efficacy

Capecitabine plus nab-paclitaxel is highly active in first-line metastatic
breast cancer
Single-Agent First-Line Therapy
New data show improved clinical activity
of nab-paclitaxel compared with docetaxel
Randomized comparison of weekly or every-3-week
(q3w) nab-paclitaxel compared to q3w docetaxel as
first-line therapy in patients (pts) with metastatic
breast cancer (MBC)
Gradishar W , et al. ASCO 2007: Abstract 1032.
Background

First generation taxanes, paclitaxel and docetaxel, provide major
improvements in treatment of early-stage and metastatic breast cancer,
but contain required chemical solvents associated with toxicity

Response rates of 40% to 60% reported in chemotherapy-naïve patients
with metastatic breast cancer treated with paclitaxel, and rates of 25% to
30% in patients refractory to anthracycline-containing regimens1

Current studies are assessing whether nab-paclitaxel can offer the same
antitumour effect as docetaxel

Previous phase III trial has demonstrated superiority of nab-paclitaxel
over paclitaxel in MBC, in addition to its advantages, which include lack
of premedication and shorter infusion time2,3

William Gradishar and colleagues presented data from fourth interim
analysis of randomized, open-label phase II study of QW or Q3W nabpaclitaxel compared to docetaxel Q3W as first-line therapy in patients
with metastatic breast cancer4
1. Nabholtz JM, et al. Expert Open Pharmacother 2000.
2. Gradishar WJ, et al. J Clin Oncol 2005.
3. Jones SE, et al. J Clin Oncol 2005.
4. Gradishar W, et al. ASCO 2007: Abstract 1032.
MBC = metastatic breast cancer
QW = weekly Q3W = every 3 weeks
Study design

This current four-arm trial compares toxicity and preliminary efficacy
data for
• Solvent-free nab-paclitaxel vs. solvent-based docetaxel
• Nab-paclitaxel QW vs. Q3W
• High-dose vs. low-dose QW nab-paclitaxel
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Study design (continued)

Patients had no prior chemotherapy for metastatic disease, Stage IV
adenocarcinoma of the breast, and adequate liver function

Three hundred patients enrolled with mean age of 54 years; 75%
were postmenopausal

Primary outcomes: antitumour response (evaluated every
8 weeks by RECIST criteria) and toxicity

Secondary outcome: PFS

Investigator-confirmed response assessments compared with
secondary response assessments conducted by independent
radiology review

Independent radiology reviewer blinded to treatment assignment,
investigator assessment of response, and target lesions identified
by investigator
MBC = metastatic breast cancer PFS= progression-free survival
Gradishar W, et al. ASCO 2007: Abstract 1032.
RECIST = response evaluation criteria in solid tumours
Key findings

The nab-paclitaxel Q3W regimen significantly improved PFS
compared with docetaxel Q3W (Figure 1)
• Nab-paclitaxel 300 mg/m2 Q3W vs. docetaxel, HR = 0.63,
p = 0.046

The nab-paclitaxel QW high-dose regimen significantly improved
PFS compared with docetaxel Q3W
• Nab-paclitaxel 150 mg/m2 QW vs. docetaxel, HR = 0.46,
p = 0.002
• Nab-paclitaxel 100 mg/m2 QW vs. docetaxel,
HR = not significant

The higher dose of weekly nab-paclitaxel (150 mg/m2 QW) was
significantly better than the lower QW dose (100 mg/m2);
HR = 0.55, p = 0.009
HR = hazard ratio
PFS= progression-free survival
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Figure 1: Progression-free survival
PFS= progression-free survival
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Figure 2: Objective response rates

Nab-paclitaxel QW (100 and 150 mg/m2) significantly increased tumour
response rate compared with docetaxel Q3W (Figure 2 above)
• nab-paclitaxel 100 mg/m2 QW vs. docetaxel 100 mg/m2 Q3W (p = 0.002)
• nab-paclitaxel 150 mg/m2 QW vs. docetaxel 100 mg/m2 Q3W (p = 0.003)
CRR = complete response rate QW = weekly Q3W = every 3 weeks
Gradishar W, et al. ASCO 2007: Abstract 1032.
RECIST = response evaluation criteria in solid tumours
Safety

Low-dose QW arm appeared to be the most tolerable of the three
nab-paclitaxel arms
• All nab-paclitaxel arms had significantly less neutropenia than
docetaxel arm
• Neutropenia (all grades) significantly more common in Q3W arm
and high-dose QW arm of nab-paclitaxel compared with low-dose
QW arm (Table 1)

Rate of febrile neutropenia lower in all nab-paclitaxel arms compared
with docetaxel

Lower incidence of fatigue with all schedules of nab-paclitaxel
compared with docetaxel (Table 2)
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Incidence of fatigue among treatment arms
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Incidence of neutropenia and febrile neutropenia
among treatment arms
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Safety (continued)

No difference observed in peripheral neuropathy rates between
nab-paclitaxel arms and docetaxel
•
The 100 mg/m2 arm of nab-paclitaxel associated with least
peripheral neuropathy

Grade 1 and 2 arthralgias significantly more common in Q3W arm
and high-dose QW arm of nab-paclitaxel compared with low-dose
QW arm

Grade 1 and 2 arthralgias more common in Q3W arm (p = 0.021)
and high-dose (150 mg/m2) QW (p = 0.048) nab-paclitaxel arms
compared with docetaxel
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Key conclusions

Response rate observed to be superior for both 100 mg/m2 and
150 mg/m2 QW doses of nab-paclitaxel compared with docetaxel
in metastatic breast cancer

PFS significantly improved with QW nab-paclitaxel 150 mg/m2 and
nab-paclitaxel 300 mg/m2 Q3W compared with docetaxel

PFS superior for QW nab-paclitaxel 150 mg/m2 compared with QW
nab-paclitaxel 100 mg/m2

Fewer AEs such as neutropenia and fatigue with all schedules
of nab-paclitaxel compared with docetaxel

Large randomized phase III trial to begin shortly comparing QW
(3 weeks out of 4) nab-paclitaxel 150 mg/m2 vs. docetaxel 100 mg/m2
Q3W in metastatic breast cancer
AE = adverse event
PFS = progression-free survival
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly Q3W = every 3 weeks
Canadian perspective by Dr. Chia

Data in this second analysis for large phase II trial interesting as
it appears more nab-paclitaxel (450 mg/m2) can be delivered
with acceptable toxicity and improved PFS compared to
docetaxel

One has to be cautious about placing too much emphasis on the
results of randomized phase II trials

Current data reaffirm nab-paclitaxel may be equivalent, if not
superior, to docetaxel in the metastatic breast cancer setting;
this finding warrants further testing of this agent in larger phase
III studies, which is set to begin

Current analysis may change schedule of nab-paclitaxel used
in phase III trials (i.e., choosing the weekly nab-paclitaxel arm
of 150 mg/m2 QW for 3 weeks out of 4)
PFS = progression-free survival
Gradishar W, et al. ASCO 2007: Abstract 1032.
QW = weekly
Combination Therapy for
First-Line Treatment
First-line data for lapatinib in HER2-positive
advanced breast cancer is encouraging
Lapatinib (L) with paclitaxel compared to paclitaxel
as first-line treatment for patients with metastatic
breast cancer: a phase III randomized, double-blind
study of 580 patients
Di Leo A, et al. ASCO 2007: Abstract 1011.
Background

In tumours of 20% to 25% of women with breast cancer HER2 gene
amplified; as many as 50 or 100 gene copies per cell generated1

Overexpression of HER2 shown to be associated with a more
aggressive disease with a poorer prognosis1

Lapatinib showed promising results in preclinical and early clinical
studies as an orally active small molecule tyrosine kinase inhibitor
that targets both HER2 and EGFR (HER1)2

Lapatinib given as a single agent results in RR of 5% to 10% in patients
with refractory disease (i.e., those who have received multiple prior
chemotherapy regimens and trastuzumab), as demonstrated in two
separate trials

Response rate appears to be approximately 25% in patients who have
not received prior treatment in the metastatic setting and who are
trastuzumab-naïve2
EGFR = epidermal growth factor receptor
1. Jørgensen JT, et al. Oncologist 2007.
HER = human epidermal growth factor receptor
2. Nelson HM, et al. Ann Pharmacother 2006.
RR = response rate
Background (continued)

Combination of lapatinib and capecitabine has received regulatory
approval by the U.S. FDA as treatment for metastatic HER2-positive
breast cancer in patients for whom other treatments have failed

This follows positive data from a pivotal open-label phase III trial in
which TTP almost doubled in patients with HER2-positive advanced
breast cancer treated with lapatinib in combination with capecitabine
vs. capecitabine alone1

Combination of lapatinib and cytotoxic capecitabine resulted in
• RR 22%, while RR to capecitabine alone was 14% (p = 0.09)
• TTP significantly better in the combination arm (8.4 mos) compared
with the single arm (4.4 mos) (p <0.001, HR = 0.47)

At ASCO 2007, Angelo Di Leo and colleagues presented a planned
subset analysis of HER2 subgroups of the phase III randomized,
double-blind, placebo-controlled, multicentre trial evaluating efficacy
and tolerability of lapatinib plus paclitaxel2
EGFR = epidermal growth factor receptor
1. Geyer CE, et al. N Engl J Med 2006.
FDA = U.S. Food and Drug Administration HR = hazard ratio
2. Di Leo A, et al. ASCO 2007: Abstract 1011.
RR = response rate TTP = time to progression
Study design

Trial enrolled 580 patients with
• Incurable HER2-negative or unknown breast cancer, Stage III or IV
• No prior treatment for metastatic disease

Median age 51 years in paclitaxel plus lapatinib arm; 52 years in
paclitaxel plus placebo arm

Majority of patients had Stage IV disease (87% and 86%, respectively)

Patients randomly assigned to receive paclitaxel 175 mg/m2 Q3W plus
either lapatinib 1,500 mg daily by mouth (n = 293) or a placebo
(n = 286); 2 patients on paclitaxel plus placebo arm received both
paclitaxel and lapatinib

Primary endpoint was TTP; study designed with 90% power to detect
40% proportional increase in median TTP of ITT population

Secondary endpoints included EFS, OS, ORR, clinical benefit rate,
ORR plus SD ≥6 months, duration of response, and safety
EFS = event-free survival ITT = intent to treat ORR = overall response rate
OS = overall survival
Di Leo A, et al. ASCO 2007: Abstract 1011.
Q3W = every 3 weeks RR = response rate
SD = stable disease TTP = time to progression
Key findings

Addition of lapatinib to paclitaxel significantly improved RR
compared with paclitaxel alone in the entire study population
(35% vs. 25%, respectively) (Table 1)

Median duration of response, OS, and EFS similar between both
treatment arms for entire study population of HER-2 negative or
unknown breast cancers
• Ninety-one patients were retrospectively identified as having
HER2-positive disease by FISH or IHC analysis of tumour
samples, 52 in the lapatinib-paclitaxel arm and 39 in the
paclitaxel-placebo arm
EFS = event-free survival
FISH = fluorescence in situ hybridization
IHC = immunohistochemistry
OS = overall survival
Di Leo A, et al. ASCO 2007: Abstract 1011.
RR = response rate
Overall outcomes of lapatinib plus paclitaxel
vs. paclitaxel alone
CI = confidence interval CR = complete response EFS = event-free survival
HR = hazard ratio ORR = overall response rate OS = overall survival
Di Leo A, et al. ASCO 2007: Abstract 1011.
PR = partial response SD = stable disease
Key findings (continued)

Findings for HER2-positive patients showed that 60% of patients
administered lapatinib plus paclitaxel experienced CR or PR, compared
to 36% given paclitaxel alone (Figure 1 below)
Di Leo A, et al. ASCO 2007: Abstract 1011.
CR = complete response HER = human epidermal growth factor receptor PR = partial response
Key findings (continued)

Median EFS significantly longer for HER2-positive patients who received
the lapatinib combination (7.9 months compared with 5.2 months in those
who received paclitaxel alone); TTP was 8.1 months compared with 5.8,
respectively (Table 2 below)
Di Leo A, et al. ASCO 2007: Abstract 1011.
EFS = event-free survival OS = overall survival
TTP = time to progression
Safety

Patients who received combination of lapatinib and paclitaxel had higher
incidence of diarrhea than those receiving paclitaxel alone, as well as
higher rate of nonprogression-related death (2.7% vs. 0.6%) (Table 3)
Di Leo A, et al. ASCO 2007: Abstract 1011.
LVEF = left ventricular ejection fraction
Key conclusions

Lapatinib in combination with paclitaxel increased PFS and EFS in firstline treatment of patients with metastatic HER2-positive breast cancer,
compared with paclitaxel alone in this relatively small subgroup of
patients

Patients with metastatic HER2-negative breast cancer do not appear to
derive additional benefit from lapatinib added to paclitaxel compared with
paclitaxel alone

Improvement in TTP came at expense of increased toxicity, particularly
diarrhea, mucositis, and rash; the latter may be related to
pharmacokinetic interactions between drugs

Authors suggest that results warrant further trials to assess predefined
molecular subtypes of breast cancer in larger randomized trials
EFS = event-free survival
HER = human epidermal growth factor receptor
PFS = progression-free survival
Di Leo A, et al. ASCO 2007: Abstract 1011.
TTP = time to progression
Canadian perspective by Dr. Chia

This study examined the combination of lapatinib with paclitaxel in
HER2-negative breast cancer for patients with metastatic breast cancer
who had no prior chemotherapy

Paclitaxel commonly used in many parts of the world where there is no
access to drugs like trastuzumab or the ability to test for HER2 status

Lapatinib blocks both HER1 and HER2 signals, so it doesn’t intrinsically
make a lot of sense to give it to HER2-negative patients. However some
HER2-negative patients have EGFR/HER1 overexpression, and that
formed the rationale for this particular study

Addition of lapatinib to paclitaxel increased RR when the whole patient
population was observed, but didn’t change TTP or OS

Benefit in EFS and TTP with lapatinib in the HER2-positive cohort, and
a trend to OS benefit
EGFR = epidermal growth factor receptor
EFS = event-free survival HER = human epidermal growth factor receptor
Di Leo A, et al. ASCO 2007: Abstract 1011.
OS = overall survival
RR = response rate TTP = time to progression
Canadian perspective (continued)

Lapatinib has only been tested in patients who have already
received trastuzumab, so this study supports the idea that
lapatinib may have similar clinical benefit as trastuzumab when
combined with a taxane in the treatment of HER2 positive MBC,
but without the associated cardiotoxicity

A positive study, overall; it will be interesting to see this drug
move forward in clinical trials and in practice

Lapatinib will be good addition to the armamentarium of agents
for metastatic breast cancer once it is approved in Canada

Cost is the issue with all new agents
HER = human epidermal growth factor receptor
Di Leo A, et al. ASCO 2007: Abstract 1011.
MBC = metastatic breast cancer
Adding a platinum to a taxane plus
trastuzumab does not add to efficacy
First overall survival analysis of a multicenter phase III
randomized trial comparing docetaxel and
trastuzumab as first-line chemotherapy for patients
with metastatic breast cancer containing the
HER2/neu alteration
Pegram M, et al. ASCO 2007: Abstract LBA1008.
Background

Trastuzumab slows the growth and spread of breast cancer cells by
binding to HER2 protein receptors and interrupting the growth signal.
In this way, trastuzumab, a monoclonal antibody, targets breast cancer
cells that overexpress the HER2 protein

Pivotal study by Dennis Slamon and colleagues compared
chemotherapy alone vs. chemotherapy plus trastuzumab1

Study demonstrated that addition of trastuzumab to chemotherapy, either
doxorubicin/cyclophosphamide (AC) or paclitaxel, improved RR, TTP,
median survival, and one-year survival rate

Improvement in survival was seen in spite of the fact that 65% of women
in the control arm ultimately received trastuzumab
HER = human epidermal growth factor receptor
1. Slamon DJ, et al. N Engl J Med 2001.
RR = response rate TTP = time to progression
Background (continued)

Results of BCIRG-007 study presented at ASCO 2006 compared
docetaxel (100 mg/m2) plus trastuzumab (TH) vs. docetaxel (75 mg/m2)
plus carboplatin plus trastuzumab (TCH) in first-line treatment of
metastatic breast cancer1
n
n
AUC = area under curve BCIRG = Breast Cancer International Research Group
FISH = fluorescence in situ hybridization HER = human epidermal growth factor receptor
1. Forbes JF, et al. J Clin Oncol 2006.
RR = response rate TTP = time to progression
Background (continued)

No difference across the two arms in
• RR (TH 72.5 % vs. TCH 72.7%)
• TTP (TH 11 months vs. TCH 10.3 months)

Both regimens appear to be acceptable

Study raised important questions about the role of platinum salt
in combination with taxane in treatment of HER2-positive
metastatic breast cancer

First overall survival analysis of the BCIRG-007 trial presented
at ASCO 20071
BCIRG = Breast Cancer International Research Group
HER = human epidermal growth factor receptor
RR = response rate TCH = carboplatin/docetaxel/trastuzumab
1. Pegram M, et al. ASCO 2007: Abstract LBA1008.
TH = docetaxel/trastuzumab TTP = time to progression
Study design

BCIRG-007 trial enrolled 263 women with FISH–confirmed,
HER2-positive metastatic breast cancer (Table 1)

Median follow-up was 39 months

Primary endpoint: TTP

Secondary endpoints: RR, duration of OR, clinical benefit, toxicity,
OS, and pathologic and molecular markers

No crossover allowed between arms

Power of the trial set to 80%, to detect 50% improvement in
median TTP

Number of events required for final analysis set at 204
(significance = 0.05, power = 0.8)
BCIRG = Breast Cancer International Research Group
FISH = fluorescence in situ hybridization
HER = human epidermal growth factor receptor
OR = overall response OS = overall survival
Pegram M, et al. ASCO 2007: Abstract LBA1008.
RR = response rate TTP = time to progression
Patient characteristics
KPS = Karnofsky Performance Status
TCH = carboplatin/docetaxel/trastuzumab
Pegram M, et al. ASCO 2007: Abstract LBA1008.
TH = docetaxel/trastuzumab
Key findings

No difference after 39 months of follow-up in survival rate of either
TH or TCH arms (39.1 months vs. 39.2 months, p = 0.65)

More patients given TCH received maximum number of chemotherapy cycles (79% versus 64%)

Grade 3 and 4 toxicities occurred with similar frequency in both
treatment arms, with the exception of thrombocytopenia, nausea,
and emesis, more common with the carboplatin-containing regimen
(Table 2, 3)

All grade sensory neuropathy, rash, myalgia, and nail changes
significantly more common in trastuzumab plus docetaxel arm
vs carboplatin-containing arm (Table 3)
TCH = carboplatin/docetaxel/trastuzumab
Pegram M, et al. ASCO 2007: Abstract LBA1008.
TH = docetaxel/trastuzumab
Reported hematological adverse events
TCH = carboplatin/docetaxel/trastuzumab
Pegram M, et al. ASCO 2007: Abstract LBA1008.
TH = docetaxel/trastuzumab
Reported non-hematological adverse events
TCH = carboplatin/docetaxel/trastuzumab
Pegram M, et al. ASCO 2007: Abstract LBA1008.
TH = docetaxel/trastuzumab
Key conclusions

Addition of carboplatin to docetaxel and trastuzumab combination
failed to improve outcomes from docetaxel plus trastuzumab alone

No statistical differences in RR, TTP, or survival between the two
treatments, though the study was underpowered to detect modest
differences

Both therapies effectively treat HER2-positive metastatic breast
cancer, with a TTP >10 months and an OS of more than 36 months

More grade 3 or 4 thrombocytopenia, nausea, and emesis in
carboplatin-containing arm

Myalgia, rash, and nail changes more common with the docetaxeltrastuzumab regimen

Because of asymmetry in the docetaxel doses (TH 100 mg/m2 vs.
TCH 75 mg/m2), it cannot be ruled out that carboplatin played a role
in response in the lower-dose docetaxel arm
HER = human epidermal growth factor receptor OS = overall survival RR = response rate
Pegram M, et al. ASCO 2007: Abstract LBA1008.
TCH = carboplatin/docetaxel/trastuzumab TH = docetaxel/trastuzumab TTP = time to progression
Canadian perspective by Dr. Chia

Application of platinum-based chemotherapy in clinical practice has
been hampered by concerns about toxicity and lack of proven
survival effects1

Some recent interest shown in combining platinums with trastuzumab,
given observed synergistic interactions in preclinical studies2

BCIRG-007 designed to study incremental effect of adding carboplatin
to proven doublets such as docetaxel and trastuzumab

First analysis of BCIRG-007 trial showed no difference in RR or PFS;
updated results show no difference in OS

Slight differences in toxicity between carboplatin-containing and noncarboplatin–containing arm suggest that women are better able to
tolerate docetaxel and trastuzumab when combined with a platinum
than without it because of the ability to deliver a lower dose of
docetaxel when combined with carboplatin
BCIRG = Breast Cancer International Research Group
1. Martin M. Clin Breast Cancer 2001.
OS = overall survival PFS = progression-free survival
2. Pegram MD, et al. J Natl Cancer Inst 2004.
RR = response rate
Capecitabine plus nab-paclitaxel is highly
active in first-line metastatic breast cancer
Phase II trial of nab-paclitaxel (nanoparticle
albumin-bound paclitaxel (ABX)) + capecitabine
(XEL) in first-line treatment of metastatic
breast cancer (MBC)
Somer B, et al. ASCO 2007: Abstract 1053.
Background

Nab-paclitaxel and capecitabine are both highly effective single agents
for the treatment of metastatic breast cancer1,2

Combination of capecitabine and taxane has been shown to improve
RR and TTP compared to singlet therapy3

Preclinical and clinical research suggests that paclitaxel enhances
activity of capecitabine4,5

Study by Somer and colleagues designed to test safety and efficacy
of nab-paclitaxel and capecitabine in novel combination schedule6
1. Gradishar WJ, et al. J Clin Oncol 2005.
2. O'Shaughnessy JA, et al. Ann Oncol 2001.
3. Miles D, et al. Clin Breast Cancer 2004.
4. Sawada N, et al. Clin Cancer Res 1998.
5. O'Shaughnessy JA, et al. Clin Breast Cancer 2006.
RR = response rate
6. Somer B, et al. ASCO 2007: Abstract 1053.
TTP = time to progression
Study design

Trial was a phase II, multicentre open-label study

Patients (n = 50) enrolled in the study (Table 1) had
•
Metastatic breast cancer, measurable by RECIST criteria,
ECOG PS 0–2, and HER2/neu negative status
•
No prior capecitabine therapy or chemotherapy for metastatic
disease
•
No adjuvant fluoropyrimidine and/or paclitaxel treatment unless
more than 6 months before enrolling in the trial if they received
these agents in the adjuvant setting

Primary objective: evaluate RR

Secondary objectives: PFS, safety, and OS

Patients received 125 mg/m2 IV nab-paclitaxel on days 1 and 8 with
no premedication, and 825 mg/m2 PO BID capecitabine on
days 1–14 Q3W
ECOG = Eastern Cooperative Oncology Group HER = human epidermal growth factor receptor
OS = overall survival PFS = progression-free survival PS = performance status
Somer B, et al. ASCO 2007: Abstract 1053.
RECIST = response evaluation criteria in solid tumours RR = response rate
Patient baseline
Somer B, et al. ASCO 2007: Abstract 1053.
Key findings

Data were available from complete sample of 50 patients

Median PFS of 270 days was observed with this combination
regimen (Figure 1)

ORR was 60.9%, with 21.5% patients exhibiting SD, and 17.4%
patients with progressive disease (Table 2)

Eight patients required a dose reduction in capecitabine;
4 patients required a dose reduction in nab-paclitaxel

Combination relatively well tolerated; most frequent grade 3
events fatigue, neutropenia, mucositis, and hand-foot syndrome
(Table 3)
ORR = overall response rate
PFS = progression-free survival
Somer B, et al. ASCO 2007: Abstract 1053.
SD = stable disease
Figure 1: Median progression-free survival
Somer B, et al. ASCO 2007: Abstract 1053.
Antitumour activity of nab-paclitaxel
plus capecitabine
Somer B, et al. ASCO 2007: Abstract 1053.
Most frequent adverse events by Common
Toxicity Criteria grade
Somer B, et al. ASCO 2007: Abstract 1053.
Key conclusions

Capecitabine plus nab-paclitaxel is highly active combination
regimen in first-line treatment of metastatic breast cancer, with
an ORR of 61%

Median PFS of 9 months observed with this combination

Dose of 125 mg/m2 nab-paclitaxel on days 1 and 8, plus 825 mg/m2
capecitabine BID on days 1−14 Q3W appears to be well tolerated
ORR = overall response rate
PFS = progression-free survival
Somer B, et al. ASCO 2007: Abstract 1053.
Q3W = every three weeks
Canadian perspective by Dr. Chia

Doublet therapy with taxanes (capecitabine or gemcitabine)
appears to be superior to monotherapy with taxanes for RR
and TTP in metastatic breast cancer (MBC)

This phase II trial demonstrated safety and efficacy for the
combination of nab-paclitaxel and capecitabine

A larger phase II trial may be needed to ensure this is a relatively
well-tolerated and active regimen in treatment of MBC, particularly
in patients already exposed to adjuvant taxane

This combination may have greater yield in the adjuvant or
neoadjuvant setting; phase III trials in these settings needed
to address whether this combination can reduce toxicity and/or
gain efficacy
RR = response rate
Somer B, et al. ASCO 2007: Abstract 1053.
TTP = time to progression