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Pertuzumab Monotherapy
Following Trastuzumab-Based
Treatment: Activity and
Tolerability in Patients with
Advanced HER2-Positive
Breast Cancer
Cortés J et al.
ASCO 2009; Abstract 1022. (Poster Discussion)
Introduction

Pertuzumab, the first in a new class of HER2 dimerization inhibitors (HDIs), is a
humanized monoclonal antibody and a potent inhibitor of HER-mediated
signaling pathways

Synergistic effects of trastuzumab and pertuzumab, thought to be driven by the
complementary mechanisms of action, have been observed in preclinical
xenograft studies

In a Phase II trial (BO17929), the combination of trastuzumab and pertuzumab
was active in two patient cohorts with HER2-positive metastatic breast cancer
(MBC) with disease progression on trastuzumab
– Objective Response Rate = 24.2% (Gelmon, ASCO 2008)

Following these promising results, the trial protocol was amended to allow
recruitment of a third cohort of patients, assessing the activity of pertuzumab
monotherapy in this clinical setting

Current study objectives:
– Investigate the safety and efficacy of pertuzumab monotherapy in patients
with HER2-positive MBC with disease progression on trastuzumab-based
therapy as part of last treatment regimen
Source: Cortés J et al. ASCO 2009;Abstract 1022.
Trastuzumab and Pertuzumab Bind
to Different Regions on HER2
HER2 receptor
Pertuzumab
Trastuzumab
Subdomain 4
of HER2
Dimerisation domain
of HER2

Trastuzumab continually
suppresses HER2 activity

Pertuzumab inhibits HER2
forming dimer pairs

Flags cells for destruction
by the immune system

Suppresses multiple HER
signalling pathways

Does not inhibit HER2
dimerization

Flags cells for destruction
by the immune system
Source: With permission from Cortés J. ASCO 2009;Abstract 1022.
BO17929: Pertuzumab
Monotherapy, Cohort 3 (N=29)
Eligibility:
• HER2-positive MBC
• ≤ 3 lines of prior
cytotoxic therapies
and/or trastuzumab
(H), including adjuvant
therapy
• Disease progression
during trastuzumab as
most recent treatment
• Study treatment
initiated > 1 month
after last dose of
trastuzumab
Cohort 3a:
Pertuzumab (P)
only (n=29)
PD*
Cohort 3b:
P+H
(n=15)
P, 840 mg loading dose  420 mg q3w
H, 4 mg/kg loading dose  2 mg/kg qw or
8 mg/kg loading dose  6 mg/kg q3w
* Trastuzumab reintroduction allowed with documented
disease progression during pertuzumab monotherapy
Results: Response and Clinical
Benefit in Study Cohort 3
Cohort 3a1
(P alone)
(n = 27*)
Cohort 3b2
(H+P, post P)
(n = 11*)
0
0
Partial response (PR)
2 (7.4)
3 (27.3)
Objective response rate (ORR)
2 (7.4)
3 (27.3)
Stable disease (SD) ≥ 6 months
1 (3.7)
0
3 (11.1)
3 (27.3)
24 (88.9)
8 (72.7)
Response, n (%)
Complete response (CR)
Clinical benefit rate
(CR + PR + SD >6 months)
Progressive disease
1
Cohort 3a: Patients in the third cohort on pertuzumab monotherapy
Cohort 3b: Patients in the third cohort who went on to receive pertuzumab and trastuzumab (H + P)
* Number of patients evaluable for overall best response at data cut-off
2
Source: Cortés J et al. ASCO 2009; Abstract 1022.
Adverse Events:
BO17929 Cohort 3

Most adverse events (AE) were grade 1/2


Most frequent: Diarrhea, nausea and vomiting
One patient experienced a treatment-related grade 3 AE
(fatigue)

Later downgraded to grade 2 unrelated to study
treatment

Mean changes in LVEF did not indicate a fall versus baseline

Three patients had a falling LVEF

None have received treatment for this event and all
were asymptomatic
Source: Cortés J et al. ASCO 2009; Abstract 1022.
Summary and Conclusions

Pertuzumab monotherapy is active in patients with
HER2-positive breast cancer with disease progression on
trastuzumab

Trastuzumab/pertuzumab combination therapy is active in
patients with disease progression on either trastuzumab or
pertuzumab monotherapy

Pertuzumab monotherapy or in combination with trastuzumab
was well tolerated. No clinically significant cardiac events were
observed in this patient group

CLEOPATRA is a Phase III trial of trastuzumab + docetaxel ±
pertuzumab in previously untreated HER2-positive metastatic
breast cancer, and is open to recruitment
Source: Cortés J et al. ASCO 2009; Abstract 1022.