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Adjuvant pertuzumab and trastuzumab in
early HER2+ breast cancer
The New England Journal of Medicine
Take-home message
•
This study investigated whether pertuzumab added to adjuvant trastuzumab and
chemotherapy would improve clinical outcomes among patients with node-positive
or high-risk node-negative HER2-positive operable breast cancer. Disease recurred
among 7.1% of patients in the pertuzumab group and 8.7% of patients in the placebo
group (HR, 0.81; P = 0.045). The 3-year rate of invasive disease-free survival in
the node-positive cohort was 92.0% with pertuzumab compared with 90.2% with
placebo (HR for an invasive-disease event, 0.77; P=0.02). The 3-year rate of invasive
disease-free survival in the node-negative cohort was 97.5% with pertuzumab and
98.4% with placebo (HR for an invasive-disease event, 1.13; P=0.64). The treatment
effect was more evident among patients at higher relapse risk because of nodal
involvement or hormone receptor-negative status, although it was homogeneous
statistically among all the subgroups.
•
The results demonstrate that pertuzumab added to trastuzumab and chemotherapy
significantly improved invasive disease-free survival rates among patients with
HER2-positive breast cancer.
Abstract
BACKGROUND
Pertuzumab increases the rate of
pathological complete response in the preop-
erative context and increases overall survival
among patients with metastatic disease when it
is added to trastuzumab and chemotherapy for
the treatment of human epidermal growth factor
receptor 2 (HER2)-positive breast cancer. In this
trial, we investigated whether pertuzumab, when
added to adjuvant trastuzumab and chemother-
apy, improves outcomes among patients with
HER2-positive early breast cancer.
METHODS
We randomly assigned patients
with node-positive or high-risk node-nega-
tive HER2-positive, operable breast cancer to
receive either pertuzumab or placebo added
to standard adjuvant chemotherapy plus 1 year
of treatment with trastuzumab. We assumed
a 3-year invasive-disease-free survival rate of
91.8% with pertuzumab and 89.2% with placebo.
RESULTS
In the trial population, 63% of the
patients who were randomly assigned to receive
pertuzumab (2400 patients) or placebo (2405
patients) had node-positive disease and 36%
had hormone-receptor-negative disease. Dis-
ease recurrence occurred in 171 patients (7.1%)
in the pertuzumab group and 210 patients (8.7%)
in the placebo group (hazard ratio, 0.81; 95%
confidence interval [CI], 0.66 to 1.00; P=0.045).
The estimates of the 3-year rates of invasive-dis-
ease-free survival were 94.1% in the pertuzumab
group and 93.2% in the placebo group. In the
cohort of patients with node-positive disease,
the 3-year rate of invasive-disease-free survival
was 92.0% in the pertuzumab group, as com-
pared with 90.2% in the placebo group (hazard
ratio for an invasive-disease event, 0.77; 95% CI,
0.62 to 0.96; P=0.02). In the cohort of patients
with node-negative disease, the 3-year rate of
invasive-disease-free survival was 97.5% in the
pertuzumab group and 98.4% in the placebo
group (hazard ratio for an invasive-disease
event, 1.13; 95% CI, 0.68 to 1.86; P=0.64). Heart
failure, cardiac death, and cardiac dysfunc-
tion were infrequent in both treatment groups.
Diarrhea of grade 3 or higher occurred almost
exclusively during chemotherapy and was more
frequent with pertuzumab than with placebo
(9.8% vs. 3.7%).
CONCLUSIONS
Pertuzumab significantly improved
the rates of invasive-disease-free survival
among patients with HER2-positive, operable
breast cancer when it was added to trastuzumab
and chemotherapy. Diarrhea was more common
with pertuzumab than with placebo.
Adjuvant pertuzumab and trastuzumab in early
HER2-positive breast cancer.
N Engl J Med
2017
Jun 05;[EPub Ahead of Print], G von Minckwitz,
M Procter, E de Azambuja, et al.
COMMENT
By Lee S. Schwartzberg
MD, FACP
D
oes dual anti-HER2 blockade
add enough benefit to justify
its use in the adjuvant setting of
HER2-positive early-stage breast can-
cer (ESBC)? The APHINITY trial tested
the addition of pertuzumab to standard
chemotherapy and 1 year of adjuvant
trastuzumab. A statistically significant
but clinically small benefit was seen at
3 years of follow-up, with a 1% improve-
ment in invasive disease-free survival
from 1 year of pertuzumab. The dis-
tant recurrence rate was also 1% better.
In subgroup analysis, node-positive
patients and ER-negative patients had
more (~2%) benefit with pertuzumab
added. On the negative side of the
ledger, pertuzumab added more all
grade and grade 3 diarrhea, and a small
increase in cardiac events.
It can be argued that, based on these
results, the decision to add pertuzumab
to a standard adjuvant regimen for
HER2-positive ESBC should be made
carefully and not indiscriminately. Cer-
tain clinically high-risk groups, such
as patients with stage III or lower
node-positive ER-negative/HER2-pos-
itive cancers appear to derive benefit
from the dual HER2 blockade. On the
other hand, smaller, stage I HER2-posi-
tive breast cancers do very well with just
12 weeks of paclitaxel and 1 year of tras-
tuzumab, as evidenced by the long-term
follow-up of the APT trial presented at
ASCO 2017; so, additional therapy is
unlikely to show a benefit.
Like in all of medicine, one size does not
fit all in the adjuvant treatment of ESBC.
Some HER2-positive patients require
dual anti-HER2 therapy, but many do
well without incremental therapy, and,
considering the additional cost and life
impact of more treatment, they should
not receive it.
Overall, pertuzumab is a small step for-
ward in HER2-positive ESBC compared
with a big jump in the first-line metastatic
setting with this drug as evidenced by
the CLEOPATRA results.
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