Long-term Clinical Outcome of Trastuzumab and Lapatinib for HER2-positive Metastatic Colorectal Cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Biomarkers, Tumor
/ analysis
Brain
/ diagnostic imaging
Brain Neoplasms
/ diagnosis
Colorectal Neoplasms
/ diagnosis
Female
Follow-Up Studies
Humans
Immunohistochemistry
Lapatinib
/ administration & dosage
Magnetic Resonance Imaging
Male
Middle Aged
Progression-Free Survival
Proto-Oncogene Proteins p21(ras)
/ genetics
Receptor, ErbB-2
/ analysis
Trastuzumab
/ administration & dosage
CNS metastases
Colorectal cancer
HER2
Lapatinib
Trastuzumab
Journal
Clinical colorectal cancer
ISSN: 1938-0674
Titre abrégé: Clin Colorectal Cancer
Pays: United States
ID NLM: 101120693
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
20
03
2020
revised:
12
06
2020
accepted:
21
06
2020
pubmed:
14
9
2020
medline:
23
11
2021
entrez:
13
9
2020
Statut:
ppublish
Résumé
ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences. Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging. A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval [CI] 3.7-6.1). Median overall survival was 10.0 months (95% CI 7.9-15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients. Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies. Clinicaltrials. Gov identifier: NCT 03225937.
Sections du résumé
BACKGROUND
ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences.
PATIENTS AND METHODS
Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging.
RESULTS
A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval [CI] 3.7-6.1). Median overall survival was 10.0 months (95% CI 7.9-15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients.
CONCLUSIONS
Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies. Clinicaltrials. Gov identifier: NCT 03225937.
Identifiants
pubmed: 32919890
pii: S1533-0028(20)30094-3
doi: 10.1016/j.clcc.2020.06.009
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers, Tumor
0
KRAS protein, human
0
Lapatinib
0VUA21238F
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
pertuzumab
K16AIQ8CTM
Trastuzumab
P188ANX8CK
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
256-262.e2Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.