Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery

Conditions

Breast Cancer

Keywords

stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IA breast cancer, stage IB breast cancer, recurrent breast cancer, stage IIIC breast cancer

Brief summary

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving trastuzumab for 6 months is as effective as giving trastuzumab for 1 year in treating patients with breast cancer. PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works when given for 6 months compared to 12 months in treating women with nonmetastatic breast cancer that can be removed by surgery.

Detailed description

OBJECTIVES: Primary * Compare the disease-free survival of women with nonmetastatic, resectable breast cancer treated with adjuvant trastuzumab (Herceptin®) for 6 months vs 12 months. Secondary * Compare cardiotoxicity in patients receiving these regimens. * Compare the cardiotoxicity and disease-free survival of patients receiving concurrent trastuzumab and chemotherapy vs sequential administration. * Correlate HER-2 polymorphism with disease-free survival/cardiotoxicity in these patients. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, modality of adjuvant chemotherapy (concurrent vs sequential), and adjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I (control arm, 12-month therapy): Patients continue to receive trastuzumab (Herceptin®) IV until a total of 12 months of therapy is completed in the absence of disease progression or unacceptable toxicity. * Arm II (experimental arm, 6-month therapy): Patients continue to receive trastuzumab\* IV until a total of 6 months of therapy is completed in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients who have already finished 6 months of trastuzumab at randomization do not receive further trastuzumab. Some patients undergo blood collection for HER-2 polymorphism analysis. After completion of study therapy, patients are followed periodically for approximately 5 years. PROJECTED ACCRUAL: A total of 7,000 patients will be accrued for this study.

Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporté I, Faure-Mercier C, Paget-Bailly S, Henriques J, Grouin JM, PHARE trial investigators.

2019-06-0694 citations

10.1016/s0140-6736(19)30653-1

Abstract GS2-07: PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer

Xavier Pivot, Gilles Romieu, Marc Debled, J-Y Pierga, Pierre Kerbrat et al. (24 authors)

Cancer Research2019-02-153 citations

10.1158/1538-7445.sabcs18-gs2-07

Fluctuation of the left ventricular ejection fraction in patients with HER2-positive early breast cancer treated by 12 months of adjuvant trastuzumab.

Jacquinot Q, Paget-Bailly S, Fumoleau P, Romieu G, Pierga JY, Espié M, Lortholary A, Nabholtz JM, Mercier CF, Pauporté I, Henriques J, Pivot X.

2018-06-1510 citations

10.1016/j.breast.2018.06.001

Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.

Curtit E, Pivot X, Henriques J, Paget-Bailly S, Fumoleau P, Rios M, Bonnefoi H, Bachelot T, Soulié P, Jouannaud C, Bourgeois H, Petit T, Tennevet I, Assouline D, Mathieu MC, Jacquin JP, Lavau-Denes S, Darut-Jouve A, Ferrero JM, Tarpin C, Lévy C, Delecroix V, Trillet-Lenoir V, Cojocarasu O, Meunier J, Pierga JY, Kerbrat P, Faure-Mercier C, Blanché H, Sahbatou M, Boland A, Bacq D, Besse C, Thomas G, Deleuze JF, Pauporté I, Romieu G, Cox DG.

2017-08-228 citations

10.1186/s13058-017-0888-4

Superimposable outcomes for sequential and concomitant administration of adjuvant trastuzumab in HER2-positive breast cancer: Results from the SIGNAL/PHARE prospective cohort.

Pivot X, Fumoleau P, Pierga JY, Delaloge S, Bonnefoi H, Bachelot T, Jouannaud C, Bourgeois H, Rios M, Soulié P, Jacquin JP, Lavau-Denes S, Kerbrat P, Cox D, Faure-Mercier C, Pauporte I, Gligorov J, Curtit E, Henriques J, Paget-Bailly S, Romieu G.

2017-06-164 citations

10.1016/j.ejca.2017.05.020

Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort.

Pivot X, Romieu G, Fumoleau P, Rios M, Bonnefoi H, Bachelot T, Soulié P, Jouannaud C, Bourgeois H, Petit T, Tennevet I, Assouline D, Mathieu MC, Jacquin JP, Lavau-Denes S, Darut-Jouve A, Ferrero JM, Tarpin C, Lévy C, Delecroix V, Trillet-Lenoir V, Cojocarasu O, Meunier J, Pierga JY, Agostini C, Kerbrat P, Faure-Mercier C, Blanché H, Sahbatou M, Boland A, Bacq D, Besse C, Calvo F, Renaud A, Deleuze JF, Pauporté I, Thomas G, Cox DG.

2017-02-231 citations

10.1038/s41523-017-0005-y

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the <i>FGFR2</i> locus and estrogen receptor status to HER2-negative breast cancer patients

David G. Cox, Elsa Curtit, Gilles Romieu, P. Fumoleau, María Rios et al. (35 authors)

Oncotarget2016-10-1414 citations

10.18632/oncotarget.12669

Abstract P6-07-13: New insights on HER2 amplification from the constitutional and somatic standpoints: Results from the ICGC and SIGNAL/Phare studies

Anne Vincent‐Salomon, Anthony Ferrari, Xavier Pivot, Gaëtan MacGrogan, Laurent Arnould et al. (18 authors)

Cancer Research2016-02-15

10.1158/1538-7445.sabcs15-p6-07-13

Cardiac toxicity events in the PHARE trial, an adjuvant trastuzumab randomised phase III study.

Pivot X, Suter T, Nabholtz JM, Pierga JY, Espie M, Lortholary A, Khayat D, Pauporte I, Romieu G, Kramar A, Fumoleau P.

2015-07-0748 citations

10.1016/j.ejca.2015.05.028

Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial.

Xavier Pivot, Thomas Bachelot, Marc Debled, Jean‐Yves Pierga, Pierre Kerbrat et al. (11 authors)

Journal of Clinical Oncology2014-05-20

10.1200/jco.2014.32.15_suppl.600

Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial.

Kramar A, Bachelot T, Madrange N, Pierga JY, Kerbrat P, Espié M, Fumoleau P, Pauporté I, Khayat D, Romieu G, Pivot X.

2014-05-1419 citations

10.1093/annonc/mdu177

6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial.

Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporté I, Kramar A, PHARE trial investigators.

2013-06-11228 citations

10.1016/s1470-2045(13)70225-0

Interventions

BIOLOGICALtrastuzumab

GENETICpolymorphism analysis

PROCEDUREadjuvant therapy

Study design

Allocation

RANDOMIZED

Primary purpose

TREATMENT

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast * Nonmetastatic disease * Positive or negative axillary nodes * Tumor size ≥ 10 mm * Resectable disease * Must have received ≥ 4 courses of chemotherapy for this disease * A 12-month adjuvant treatment with trastuzumab (Herceptin®) has been initiated * Informed consent form must be signed between the third and sixth months of trastuzumab therapy * Overexpression of HER-2 in the invasive component of the primary tumor as indicated by 1 of the following: * 3+ by immunohistochemistry (IHC) * 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Female * Menopausal status not specified * LVEF considered favorable for continuing trastuzumab treatment as measured by echocardiography or MUGA at 2-4 months after beginning adjuvant trastuzumab * No serious cardiac illness or medical condition precluding trastuzumab treatment, including any of the following: * History of documented congestive heart failure * High-risk uncontrolled arrhythmias * Angina pectoris requiring antianginal medication * Severe dyspnea at rest or oxygen-dependent * No known hypersensitivity to trastuzumab, murine proteins, or any of the excipients * Not pregnant or nursing * No social, geographical, or psychological condition that would preclude study participation PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Other prior anti-HER-2 therapy allowed * No prior trastuzumab other than initiation of trastuzumab adjuvant therapy

Design outcomes

Primary

Measure	Time frame
Time to recurrence	—

Secondary

Measure	Time frame
Cardiotoxicity as measured by LVEF	—
Distant metastasis-free survival	—
Overall survival	—

Countries

France

Outcome results

None listed