Download Pertuzumab + trastuzumab

Premio Galeno 2015
Candidatura ROCHE S.p.A.
PERJETA
420 mg concentrate for solution for infusion
pertuzumab
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Perjeta: Therapeutic indications
Metastatic Breast Cancer
Perjeta is indicated for use in combination with trastuzumab and docetaxel in
adult patients with HER2-positive metastatic or locally recurrent unresectable
breast cancer, who have not received previous anti-HER2 therapy or
chemotherapy for their metastatic disease.
Available in Italy from June 2014
Innovation status granted by AIFA
More than 1000 patients treated to date
Neoadjuvant Treatment of Breast Cancer
Perjeta is indicated for use in combination with trastuzumab and chemotherapy for the
neoadjuvant treatment of adult patients with HER2-positive, locally advanced,
inflammatory, or early stage breast cancer at high risk of recurrence
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HER2 overexpression
a negative prognostic factor in breast cancer
HER2-positive tumors and high serum HER2 levels correlate with
aggressive breast tumor behaviour1
 Disease recurrence
 Metastasis
 Shortened survival
 Rapid tumor development
 High nuclear grade
 Ductal versus lobular status.
HER2 overexpression/HER2 gene amplification occurs in around
18–20% of breast cancers.2
1.
2.
Ross JS, Fletcher JA, Linette GP, et al. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 2003; 8(4): 307-325.
Wolff AC, Hammond EH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human
epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007; 131(1): 18-43.
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Pertuzumab is the first
in a new class of HER2 dimerisation inhibitors
•
Key HER signalling pathways that mediate cancer cell proliferation and survival are
inhibited by pertuzumab blockade of HER2 dimerisation.1–4
•
In addition, pertuzumab can activate antibody-dependent cellular 5cytotoxicity.5
Pertuzumab
HER1, 3, is
4 the first inHER2
Pertuzumab
a new class
of HER2 dimerisation inhibitors
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For personal use only
Graphical elaboration from text data.
1. Agus DB, et al. Cancer Cell 2002; 2(2): 127-137; 2. Hughes JB, et al. Mol Cancer Ther 2009; 8(7): 1885-1892; 3. Baselga J. Cancer Cell 2002; 2(2): 9395; 4. Franklin MC, et al. Cancer Cell 2004; 5(4): 317-328; 5. Scheuer W, et al. Cancer Res 2009; 69(24): 9330-9336.
Pertuzumab and trastuzumab
bind to different domains on HER2 and have
complementary mechanisms of action
•
•
•
Pertuzumab binds to subdomain II and inhibits ligand-dependent signalling.1
Trastuzumab binds to subdomain IV and inhibits ligand-independent intracellular
signalling.2
The pertuzumab–trastuzumab combination offers a more comprehensive HER2
blockade3,4
– The same MOA principles apply toPertuzumab
pertuzumab–T-DM1 combination.5
HER1, 3, 4
HER2
Trastuzumab
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For personal use only
Graphical elaboration from text data.
1. Franklin MC, et al. Cancer Cell 2004; 5(4): 317-328; 2. Junttila TT, et al. Cancer Cell 2009; 15(5): 429-440; 3. Nahta R, et al. Cancer Res 2004; 64(7):
2343-2346; 4. Scheuer W, et al. Cancer Res 2009; 69(24): 9330-9336; 5. Fields C, et al. AACR 2010. Abstract 5607.
CLEOPATRA: Phase III trial of trastuzumab plus
docetaxel with or without pertuzumab
n = 406
Placebo + trastuzumab
Docetaxel*
≥6 cycles recommended
Patients with
HER2-positive MBC
centrally confirmed
(N = 808)
1:1
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Pertuzumab + trastuzumab
n = 402


Docetaxel*
≥6 cycles recommended
*<6 cycles allowed for unacceptable toxicity or PD;
>6 cycles allowed at investigator’s discretion
Randomisation was stratified by geographic region and prior treatment status
([neo]adjuvant chemotherapy received or not).
Study dosing q3w:
– Pertuzumab/placebo:
– Trastuzumab:
– Docetaxel:
840 mg loading dose, 420 mg maintenance
8 mg/kg loading dose, 6 mg/kg maintenance
75 mg/m2, escalating to 100 mg/m2 if tolerated
PD, progressive disease; R, randomised.
Baselga J, et al. N Engl J Med 2012; 366(2): 109-119 (study protocol can be found online with the publication).
*This article is copyrighted by the Massachusetts Medical Society. All rights reserved. It is provided for your personal informational use only.
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CLEOPATRA:
Overall survival (%)
Patients lived 15.7 months longer when treated with
P + H + T vs. H + T alone in final OS analysis
100
PHT: 168 events; median 56.5 months
90
HT: 221 events; median 40.8 months
80
70
60
50
HR 0.68
95% CI = 0.56, 0.84
p = 0.0002
40
30
Δ 15.7 months
20
10
0
0
10
20
30
40
50
60
70
104
91
28
23
1
0
Time (months)
n at risk
PHT
402
HT
406
371
350
318
289
268
230
Data cut-off: February 2014.
CI, confidence interval; H, trastuzumab; HR, hazard ratio; P, pertuzumab; T, docetaxel.
Adapted from Swain SM, et al. ESMO 2014 (Abstract 350O_PR).
226
179
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NeoSphere:
Phase II study of pertuzumab in the neoadjuvant
setting
Neoadjuvant treatment
q3w x 4
Adjuvant treatment
Trastuzumab + docetaxel (n = 107)
Trastuzumab + FEC
Arm A
S
N = 417
Arm B
Pertuzumab + trastuzumab
+ docetaxel (n = 107)
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U
R
Trastuzumab + FEC
G
Arm C
E
Pertuzumab + trastuzumab (n = 107)
Arm D
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Trastuzumab + [docetaxel  FEC]
Y
Pertuzumab + docetaxel (n = 96)
Gianni L, et al. Lancet Oncol 2012; 13(1): 25-32. (study protocol available with the publication online).
Trastuzumab + FEC
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NeoSphere:
Pertuzumab and trastuzumab plus docetaxel
significantly increased the pCR rate vs. other arms
p = 0.0198
p = 0.0141
50
p = 0.003
pCR, %  95% CI
40
45.8
30
20
29.0
24.0
10
16.8
0
n = 107
n = 107
n = 107
n = 96
Arm A
Arm B
Arm C
Arm D
HT
PHT
PH
PT
H, trastuzumab; P, pertuzumab; pCR, pathological complete response; T, docetaxel.
Gianni et al. Oral presentation SABCS 2011- available at http://sabcs11.m2usa.com/sabcs.html - Last access October 2013; Gianni L, et al. Lancet Oncol
2012; 13(1): 25-32.
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Doing now what patients need next
Grazie dell’attenzione!