N083E (Alliance): long-term outcomes of patients treated in a pilot phase II study of docetaxel, carboplatin, trastuzumab, and lapatinib as adjuvant therapy for early-stage HER2-positive breast cancer.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Breast Neoplasms
/ drug therapy
Carboplatin
/ administration & dosage
Carcinoma, Ductal, Breast
/ drug therapy
Carcinoma, Lobular
/ drug therapy
Docetaxel
/ administration & dosage
Female
Follow-Up Studies
Humans
Lapatinib
/ administration & dosage
Middle Aged
Neoadjuvant Therapy
Pilot Projects
Prognosis
Receptor, ErbB-2
/ metabolism
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Survival Rate
Trastuzumab
/ administration & dosage
Adjuvant
Breast cancer
Gastrointestinal
HER2 cardiac
Lapatinib
Tolerability
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
21
04
2020
accepted:
26
05
2020
pubmed:
7
6
2020
medline:
5
2
2021
entrez:
7
6
2020
Statut:
ppublish
Résumé
The addition of lapatinib (L) to trastuzumab (T) was previously found to be synergistic in preclinical models and in the neoadjuvant setting. Prior to the results of the ALTTO trial, this study assessed the safety and feasibility of adding L to the standard adjuvant docetaxel, carboplatin, and trastuzumab (TCH) regimen in early-stage HER2-positive breast cancer (HER2+ BC). In this single-arm, 2-stage, phase II study, patients with stages I-III HER2+ BC received TCH plus L at 1000 mg daily for a total of 12 months. The primary endpoint was the safety and tolerability, including the rate of diarrhea. Secondary endpoints included adverse event (AE) profile using the NCI CTCAE v3.0 and cardiac safety. Thirty eligible patients were enrolled. Median follow-up is 5.3 years. Diarrhea was the most common AE with 50% Grade (G)1/2 and 43% G3 diarrhea. However, it was responsive to dose reduction of L (750 mg) and institution of anti-diarrheal medications. Cardiovascular AE were infrequent and no patients experienced congestive heart failure while on treatment. TCHL was a tolerable regimen at a starting L dose of 750 mg PO daily when given concurrently with chemotherapy.
Sections du résumé
BACKGROUND
The addition of lapatinib (L) to trastuzumab (T) was previously found to be synergistic in preclinical models and in the neoadjuvant setting. Prior to the results of the ALTTO trial, this study assessed the safety and feasibility of adding L to the standard adjuvant docetaxel, carboplatin, and trastuzumab (TCH) regimen in early-stage HER2-positive breast cancer (HER2+ BC).
METHODS
In this single-arm, 2-stage, phase II study, patients with stages I-III HER2+ BC received TCH plus L at 1000 mg daily for a total of 12 months. The primary endpoint was the safety and tolerability, including the rate of diarrhea. Secondary endpoints included adverse event (AE) profile using the NCI CTCAE v3.0 and cardiac safety.
RESULTS
Thirty eligible patients were enrolled. Median follow-up is 5.3 years. Diarrhea was the most common AE with 50% Grade (G)1/2 and 43% G3 diarrhea. However, it was responsive to dose reduction of L (750 mg) and institution of anti-diarrheal medications. Cardiovascular AE were infrequent and no patients experienced congestive heart failure while on treatment.
CONCLUSION
TCHL was a tolerable regimen at a starting L dose of 750 mg PO daily when given concurrently with chemotherapy.
Identifiants
pubmed: 32504284
doi: 10.1007/s10549-020-05709-z
pii: 10.1007/s10549-020-05709-z
pmc: PMC7535136
mid: NIHMS1609961
doi:
Substances chimiques
Receptors, Estrogen
0
Receptors, Progesterone
0
Lapatinib
0VUA21238F
Docetaxel
15H5577CQD
Carboplatin
BG3F62OND5
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
613-622Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002379
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189812
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189808
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA025224
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA035103
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA035415
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA063849
Pays : United States
Références
Br J Cancer. 1992 Jan;65(1):118-21
pubmed: 1346366
Oncologist. 1998;3(4):237-252
pubmed: 10388110
J Clin Oncol. 2010 Mar 1;28(7):1124-30
pubmed: 20124187
Lancet Oncol. 2011 Mar;12(3):236-44
pubmed: 21354370
Br J Cancer. 1991 Mar;63(3):447-50
pubmed: 1672256
Lancet Oncol. 2017 Dec;18(12):1688-1700
pubmed: 29146401
J Clin Oncol. 2016 Apr 1;34(10):1034-42
pubmed: 26598744
Oncogene. 2002 Sep 12;21(41):6255-63
pubmed: 12214266
N Engl J Med. 2019 Feb 14;380(7):617-628
pubmed: 30516102
N Engl J Med. 2006 Dec 28;355(26):2733-43
pubmed: 17192538
Lancet. 2012 Feb 18;379(9816):633-40
pubmed: 22257673
Biostatistics. 2012 Apr;13(2):204-16
pubmed: 22285995
N Engl J Med. 2005 Oct 20;353(16):1659-72
pubmed: 16236737
J Clin Oncol. 2011 Sep 1;29(25):3366-73
pubmed: 21768458
Breast Cancer Res Treat. 2013 Apr;138(2):427-35
pubmed: 23479422
Science. 1987 Jan 9;235(4785):177-82
pubmed: 3798106
J Clin Oncol. 2008 Jul 10;26(20):3317-23
pubmed: 18490651
Breast Cancer Res Treat. 1992;24(2):85-95
pubmed: 8095168
N Engl J Med. 2017 Jul 13;377(2):122-131
pubmed: 28581356
J Clin Oncol. 2010 Jun 20;28(18):2982-8
pubmed: 20479410
Arch Pathol Lab Med. 2007;131(1):18-43
pubmed: 19548375
Nature. 2012 Apr 04;486(7403):395-9
pubmed: 22495314
Science. 1985 Dec 6;230(4730):1132-9
pubmed: 2999974
N Engl J Med. 2005 Oct 20;353(16):1673-84
pubmed: 16236738
N Engl J Med. 2011 Oct 6;365(14):1273-83
pubmed: 21991949