Neoadjuvant dual HER2-targeted therapy with lapatinib and trastuzumab improves pathologic complete response in patients with early stage HER2-positive breast cancer: a meta-analysis of randomized prospective clinical trials.
BACKGROUND
Randomized clinical trials (RCT) that evaluated the addition of lapatinib to trastuzumab plus neoadjuvant chemotherapy (NAC) in patients with HER2-positive, operable breast cancer revealed a questionable improvement in pathologic complete response (pCR) rate. We performed a meta-analysis of prospective RCTs that examined the effect of adding lapatinib to trastuzumab and NAC on pCR rate.


METHODS
PubMed databases and abstracts from the proceedings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were searched for RCTs that compared lapatinib plus trastuzumab and NAC with trastuzumab in combination with NAC and that included pCR as the primary outcome. Our main objective was to estimate the effect of adding lapatinib to trastuzumab plus NAC on pCR rate, defined as no residual invasive cancer in breast and axillary lymph nodes.


RESULTS
In total, 1,017 patients with early stage breast cancer from 5 trials were included. Four trials examined the addition of lapatinib to trastuzumab plus NAC; this resulted in statistically significant improvement in pCR, defined as no residual carcinoma in breast and lymph nodes. The pCR rate was 55.76% and 38.36% in the lapatinib plus trastuzumab and the trastuzumab plus NAC arms, respectively (odds ratio [OR]: 1.94; 95% confidence interval [CI]: 1.44-2.60). In three trials, the rates of pCR, defined as no residual invasive carcinoma in breast only, for the lapatinib plus trastuzumab and trastuzumab-alone groups were 55.01% and 40.70%, respectively, also resulting in significant improvement (OR: 1.78; 95% CI: 1.27-2.50).


CONCLUSIONS
The addition of lapatinib to trastuzumab in combination with neoadjuvant chemotherapy significantly improves pCR rates in patients with HER2-positive breast cancer.
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Mellissa
M
Hicks
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Erin R
ER
Macrae
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Mahmoud
M
Abdel-Rasoul
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Rachel
R
Layman
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Susan
S
Friedman
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Jenny
J
Querry
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Maryam
M
Lustberg
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Bhuvaneswari
B
Ramaswamy
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Ewa
E
Mrozek
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Charles
C
Shapiro
The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA Robert.Wesolowski@osumc.edu.
Robert
R
Wesolowski
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008198:Lymph Nodes / Q000473:pathology; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D017594:Publication Bias; D011799:Quinazolines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome
D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Breast cancer; HER2; Lapatinib; Meta-analysis; Neoadjuvant chemotherapy; Trastuzumab