Abstract
Introduction: Human epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits. Objective: We evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population. Patients and Methods: We identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016. Results: Median age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference. Conclusions: First line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.
References
1.
Swain
SM
, Baselga
J
, Kim
SB
, Ro
J
, Semiglazov
V
, Campone
M
, et al.; CLEOPATRA Study Group
. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer
. [Internet]
. N Engl J Med
. 2015
Feb
;372
(8
):724
–34
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25693012
[PubMed]
0028-47932.
Baselga
J
, Cortés
J
, Kim
SB
. Im S-A, Hegg R, Im Y-H, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med [Internet]. 2012
Jan 12;366(2):109–19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/221498753.
Swain
SM
, Kim
SB
, Cortés
J
, Ro
J
, Semiglazov
V
, Campone
M
, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study
. [Internet]
. Lancet Oncol
. 2013
May
;14
(6
):461
–71
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23602601
[PubMed]
1470-20454.
Alsayed
A
, Badran
A
, Elashwah
A
, Gad
A
, Shahin
A
, Omar
A
, et al. Efficacy, Safety Profiles and Outcomes of Dual Anti Her2 Blockade in Combination with Neoadjuvant Chemotherapy in Locally Advanced (Stage II-III) Her2 Expressing Breast Cancer Patients, Middle East Experience. Pan Arab J Oncol [Internet]. 2018;2(November 2018
). Available from: www.amaac.org5.
Nishino
M
, Jagannathan
JP
, Ramaiya
NH
, Van den Abbeele
AD
. Revised RECIST guideline version 1.1: what oncologists want to know and what radiologists need to know
. [Internet]
. AJR Am J Roentgenol
. 2010
Aug
;195
(2
):281
–9
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20651182
[PubMed]
0361-803X6.
Carlson
RW
, Moench
SJ
, Hammond
ME
, Perez
EA
, Burstein
HJ
, Allred
DC
, et al.; NCCN HER2 Testing in Breast Cancer Task Force
. HER2 testing in breast cancer: NCCN Task Force report and recommendations
. [Internet]
. J Natl Compr Canc Netw
. 2006
Jul
;4
Suppl 3
:S1
–22
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16813731
[PubMed]
1540-14057.
Slamon
DJ
, Leyland-Jones
B
, Shak
S
, Fuchs
H
, Paton
V
, Bajamonde
A
, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2
. [Internet]
. N Engl J Med
. 2001
Mar
;344
(11
):783
–92
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11248153
[PubMed]
0028-47938.
Marty
M
, Cognetti
F
, Maraninchi
D
, Snyder
R
, Mauriac
L
, Tubiana-Hulin
M
, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group
. [Internet]
. J Clin Oncol
. 2005
Jul
;23
(19
):4265
–74
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15911866
[PubMed]
0732-183X9.
Robert
NJ
, Goertz
HP
, Chopra
P
, Jiao
X
, Yoo
B
, Patt
D
, et al. HER2-Positive Metastatic Breast Cancer Patients Receiving Pertuzumab in a Community Oncology Practice Setting: Treatment Patterns and Outcomes
. [Internet]
. Drugs Real World Outcomes
. 2017
Mar
;4
(1
):1
–7
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28063028
[PubMed]
2199-115410.
De Placido
S
, Giuliano
M
, Schettini
F
, Von Arx
C
, Buono
G
, Riccardi
F
, et al. Human epidermal growth factor receptor 2 dual blockade with trastuzumab and pertuzumab in real life: italian clinical practice versus the CLEOPATRA trial results
. [Internet]
. Breast
. 2018
Apr
;38
:86
–91
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29287189
[PubMed]
0960-977611.
Assi
HA
, Khoury
KE
, Dbouk
H
, Khalil
LE
, Mouhieddine
TH
, El Saghir
NS
. Epidemiology and prognosis of breast cancer in young women
. [Internet]
. J Thorac Dis
. 2013
Jun
;5
Suppl 1
:S2
–8
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23819024
[PubMed]
2072-143912.
Han
W
, Kim
SW
, Park
IA
, Kang
D
, Kim
SW
, Youn
YK
, et al. Young age: an independent risk factor for disease-free survival in women with operable breast cancer
. [Internet]
. BMC Cancer
. 2004
Nov
;4
(1
):82
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15546499
[PubMed]
1471-240713.
Bachelot
T
, Ciruelos
E
, Schneeweiss
A
, Puglisi
F
, Peretz-Yablonski
T
, Bondarenko
I
, et al. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann Oncol Off J Eur Soc Med Oncol [Internet]. 2019
May 1;30(5):766–73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3079682114.
Al-Nozha
MM
, Arafah
MR
, Al-Mazrou
YY
, Al-Maatouq
MA
, Khan
NB
, Khalil
MZ
, et al. From the Department of Medicine (Coronary artery disease in Saudi Arabia. 2004
;966(April):1165–71. Available from: www.smj.org.sa15.
Di
D
. WHO | Noncommunicable diseases country profiles 2011. 2011
;209. Available from: http://www.who.int/nmh/publications/ncd_profiles2011/en/index.html#.UbNQMyMkAnQ.mendeley16.
Savci-Heijink
CD
, Halfwerk
H
, Hooijer
GK
, Horlings
HM
, Wesseling
J
, van de Vijver
MJ
. Retrospective analysis of metastatic behaviour of breast cancer subtypes
. [Internet]
. Breast Cancer Res Treat
. 2015
Apr
;150
(3
):547
–57
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25820592
[PubMed]
0167-680617.
Onitilo
AA
, Engel
JM
, Greenlee
RT
, Mukesh
BN
. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival
. [Internet]
. Clin Med Res
. 2009
Jun
;7
(1-2
):4
–13
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19574486
[PubMed]
1539-418218.
Murthy
RK
, Varma
A
, Mishra
P
, Hess
KR
, Young
E
, Murray
JL
, et al. Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with HER2-positive metastatic breast cancer
. [Internet]
. Cancer
. 2014
Jul
;120
(13
):1932
–8
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24677057
[PubMed]
0008-543X19.
Baselga
J
, Swain
SM
. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3
. [Internet]
. Nat Rev Cancer
. 2009
Jul
;9
(7
):463
–75
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19536107
[PubMed]
1474-175X20.
Cortés
J
, Fumoleau
P
, Bianchi
GV
, Petrella
TM
, Gelmon
K
, Pivot
X
, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer
. [Internet]
. J Clin Oncol
. 2012
May
;30
(14
):1594
–600
. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22393084
[PubMed]
0732-183X21.
Swain
SM
, Miles
D
, Kim
SB
. Im Y-H, Im S-A, Semiglazov V, et al. End-of-study analysis from the phase III, randomized, double-blind, placebo (Pla)-controlled CLEOPATRA study of first-line (1L) pertuzumab (P), trastuzumab (H), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC). J Clin Oncol [Internet]. 2019
May 20;37(15_suppl):1020–1020. Available from: https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.1020© 2020 S. Karger AG, Basel
2020
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