A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.

A Randomized, Open Label Study to Compare the Complete Pathological Response Rate Achieved With 4 Combinations of Herceptin, Docetaxel and Pertuzumab in Patients With Locally Advanced, Inflammatory or Early Stage HER2 Positive Breast Cancer

This 4 arm study will evaluate the efficacy and safety of 4 neoadjuvant treatment regimens in female patients with locally advanced, inflammatory or early stage HER2 positive breast cancer. Before surgery, patients will be randomized to one of 4 treatment arms, to receive 4 cycles of a)Herceptin + docetaxel b)Herceptin + docetaxel + pertuzumab c)Herceptin + pertuzumab or 4)pertuzumab + docetaxel. Pertuzumab will be administered at a loading dose of 840mg iv, then 420mg iv 3-weekly, Herceptin at a loading dose of 8mg/kg iv then 6mg/kg 3-weekly, and docetaxel at a dose of 75mg/m2 escalating to 100mg/m2 3-weekly. During the entire pre- and post-surgery period all patients will receive adequate chemotherapy as per standard of care, as well as any surgery and/or radiotherapy as required. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Herceptin; Drug: Docetaxel; Drug: Pertuzumab

• Study Type: Interventional
• Enrollment (Actual): 417
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Geelong Hospital; Andrew Love Cancer Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Mount Medical Center
• Austria
  • Vienna, Austria, 1100
    • Kaiser Franz Josef Spital; Iii. Medizinische Abt. Mit Onkologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I
• Brazil
  • RS
    • Ijui, RS, Brazil, 98700-000
      • Hospital de Caridade de Ijui; Oncologia
    • Porto Alegre, RS, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição
  • SC
    • Itajai, SC, Brazil, 88301-220
      • Clínica de Neoplasias Litoral
  • SP
    • Jau, SP, Brazil, 17210-080
      • Hospital Amaral Carvalho
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
    • Sao Paulo, SP, Brazil, 01317-000
      • Hospital Perola Byington
    • Sao Paulo, SP, Brazil, 01221-020
      • Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica
    • Sao Paulo, SP, Brazil, 03102-002
      • Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
    • Sorocaba, SP, Brazil, 18030-245
      • Instituto de Oncologia de Sorocaba - CEPOS
• Canada
  • Quebec, Canada, G1S 4L8
    • CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital
  • Ontario
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario; Kingston General Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University; Montreal General Hosptial; Oncology
• Israel
  • Jerusalem, Israel, 91120-01
    • Hadassah Ein Karem Hospital; Oncology Dept
  • Kfar-Saba, Israel, 4428164
    • Meir Medical Center; Oncology
  • Tel Aviv, Israel, 6423906
    • Sourasky / Ichilov Hospital; Dept. of Oncology
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli
    • Parma, Emilia-Romagna, Italy, 43100
      • Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
  • Lombardia
    • Legnano, Lombardia, Italy, 20025
      • ASST OVEST MILANESE; Oncologia Medica
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele, Servizio di Oncologia e Chemioterapia
  • Veneto
    • Mirano, Veneto, Italy, 30035
      • Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica
    • Santorso, Veneto, Italy, 36014
      • Polo Ospedaliero Santorso
    • Vicenza, Veneto, Italy, 36100
      • Ospedale Di Vicenza; Nefrologia, Oncologia Medica
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Centre; Division of Hematology/Oncology
• Mexico
  • Aguascalientes, Mexico, 20230
    • Hospital Miguel Hidalgo
  • Mexico City, Mexico, 06700
    • ARKE Estudios Clínicos S.A. de C.V.
  • Puebla, Mexico, 72530
    • Issstep Puebla, ; Oncology
• Peru
  • Arequipa, Peru, 5154
    • Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica
  • Lima, Peru, 11
    • Hospital Nacional Edgardo Rebagliati Martins; Oncologia
• Poland
  • Lublin, Poland, 20-090
    • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej
  • Olsztyn, Poland, 10-513
    • Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.
  • Poznan, Poland, 60-569
    • Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
  • Poznan, Poland, 61-485
    • NZOZ Centrum Medyczne HCP Sp. z o.o.
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
  • Warszawa, Poland, 00-909
    • Central Hospital of Military School of Medicine; Oncology
• Russian Federation
  • Kazan, Russian Federation, 420111
    • SI of Healthcare Kazan Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
  • Moscow, Russian Federation, 129128
    • NSI of Healthcare Central Clinical Hospital #2 n.a. N.A.Semashko of the Russian Railways
  • Petrozavodsk, Russian Federation, 185007
    • State Institution Of Healthcare Republican Oncology Dispensary
  • Pyatigorsk, Russian Federation, 357502
    • State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
  • Ryazan, Russian Federation, 390011
    • SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
  • Samara, Russian Federation, 443031
    • SBI of Healthcare Samara Regional Clinical Oncology Dispensary
  • Soshi, Russian Federation, 354057
    • SI of HealthCare Oncologic Dispensary #2 of department of healthcare of Krasnodar region
  • St Petersburg, Russian Federation, 191104
    • SBI of Healthcare Leningrad Regional Oncology Dispensary
  • Ulyanovsk, Russian Federation, ND
    • Ulyanovsk Regional Oncology Dispensary; Chemotherapy
  • Leningrad
    • St Petersburg, Leningrad, Russian Federation, 197758
      • FSBI "Scientific Research Institute of Oncology named after N.N.Petrov" Ministry of Health of RF
• Spain
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet; Servicio Oncologia
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Oncologia
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska Hospital; Oncology - Radiumhemmet
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset, Onkologkliniken
• Switzerland
  • Baden, Switzerland, 5405
    • Kantonsspital Baden; Frauenklinik
  • Zürich, Switzerland, 8008
    • BrustZentrum
• Taiwan
  • Taipei, Taiwan, 00112
    • VETERANS GENERAL HOSPITAL; Department of General Surgery
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Songkhla, Thailand, 90110
    • Prince of Songkla Uni ; Unit of Medical Oncology
• Turkey
  • Izmir, Turkey, 35340
    • Dokuz Eylul Uni Medical Faculty; Oncology Dept
  • Sıhhiye, ANKARA, Turkey, 06100
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Walsgrave Hospital; Dept of Oncology
  • Manchester, United Kingdom, M20 4QL
    • Christie Hospital; Breast Cancer Research Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female patients, >=18 years of age;
• locally advanced, inflammatory or early stage invasive breast cancer;
• HER2 positive (HER2+++ by IHC or FISH/CISH+).

Exclusion Criteria:

• metastatic disease (Stage IV) or bilateral breast cancer;
• previous anticancer therapy or radiotherapy for any malignancy;
• other malignancy, other than cancer in situ of the cervix, or basal cell cancer;
• insulin-dependent diabetes;
• clinically relevant cardiovascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Herceptin; 8mg/kg iv loading dose, followed by 6mg/kg iv 3-weekly; Other Names: Trastuzumab; Drug: Docetaxel; 75mg/m2 iv escalating to 100mg/m2 iv 3-weekly
Experimental: 2	Drug: Herceptin; 8mg/kg iv loading dose, followed by 6mg/kg iv 3-weekly; Other Names: Trastuzumab; Drug: Docetaxel; 75mg/m2 iv escalating to 100mg/m2 iv 3-weekly; Drug: Pertuzumab; 840mg iv loading dose, followed by 420mg iv 3-weekly
Experimental: 3	Drug: Herceptin; 8mg/kg iv loading dose, followed by 6mg/kg iv 3-weekly; Other Names: Trastuzumab; Drug: Pertuzumab; 840mg iv loading dose, followed by 420mg iv 3-weekly
Experimental: 4	Drug: Docetaxel; 75mg/m2 iv escalating to 100mg/m2 iv 3-weekly; Drug: Pertuzumab; 840mg iv loading dose, followed by 420mg iv 3-weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Pathological Complete Response (pCR)	pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders	Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Percentage of Participants Achieving pCR by Breast Cancer Type	pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Based on the type of breast cancer participants were categorized as those with 1. Operable breast cancer, 2. Inflammatory breast cancer and 3. Locally advanced breast cancer. Participants with invalid/missing pCR assessments were defined as non-responders.	Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Percentage of Participants Achieving pCR by Hormone Receptor Status	pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants were classified as Estrogen and/or Progesterone positive (+ve), Estrogen and/or Progesterone negative (-ve) or receptor status unknown. Participants with invalid/missing pCR assessments were defined as non-responders.	Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Percentage of Participants Achieving pCR by Lymph Node Status	pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Lymph node status was defined as either negative lymph node at surgery or positive lymph node at surgery. Participants with invalid/missing pCR assessments were defined as non-responders.	Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)	pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders.	Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography	Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is greater than (>)0 at screening or cycle 1 Day 1; PR: if measurement is at least a 30 percent (%) decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline.	Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography	Tumor assessments were made based on the RECIST criteria - version 1.0 The overall response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination	Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination	Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography	Clinical response was determined based on tumor measurements by sponsor in combination with tumor response assessment by investigator. Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Overall response is derived based on the sum total of breast tumors and all nodes examined.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination	Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Primary breast tumor clinical response is based on primary breast tumor assessment. Overall response is derived based on the sum total of breast tumors and all nodes examined.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Time to Clinical Response During Neo-Adjuvant Treatment Period	Time to clinical response was defined as the time from the date of first dose received to the date of assessment of clinical response. Time to Clinical response was determined by Kaplan-Meier estimates. Tumor assessments were made based on the RECIST criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period	Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: PD: if lesion is at least a 20 % increased from measurements at baseline. Percentage of participants along with 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method were reported. Missing investigator assessments were considered as no progressive disease.	Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned	Breast Conserving Surgery (BCS) was defined as quadrantectomy, lumpectomy, no surgery, sentinel node biopsy, axillary surgical resection or other method of avoiding mastectomy.	Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months
Percentage of Participants Who Were Progression Free and Disease Free	Disease-free survival (DFS) was defined as the time from first date of no disease to first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from the study without documented progression and for whom evaluations were made, were censored at date of last assessment when participant was known to be disease-free. Progression-free survival (PFS) was defined as time from date of randomization to first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from study without documented progression and for whom evaluations were made, were censored at date of last assessment when the participant was known to be free from progressive disease. Participants without post baseline assessments but known to be alive were censored at the time of randomization.	Randomization up to a maximum of 329 weeks
Progression Free and Disease Free Survival	DFS was defined as the time from the first date of no disease (date of surgery) to the first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. PFS was defined as the time from the date of randomization to the first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. DFS and PFS were determined using Kaplan-Meier estimates.	Randomization up to a maximum of 329 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Bianchini G, Kiermaier A, Bianchi GV, Im YH, Pienkowski T, Liu MC, Tseng LM, Dowsett M, Zabaglo L, Kirk S, Szado T, Eng-Wong J, Amler LC, Valagussa P, Gianni L. Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer. Breast Cancer Res. 2017 Feb 9;19(1):16. doi: 10.1186/s13058-017-0806-9.
• Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol. 2017 Apr 1;28(4):761-768. doi: 10.1093/annonc/mdw695. Erratum In: Ann Oncol. 2018 Apr 1;29(4):1075. Ann Oncol. 2018 Jul 1;29(7):1607. Ann Oncol. 2019 Aug 1;30(8):1404.
• Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzu D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. doi: 10.1016/S1470-2045(16)00163-7. Epub 2016 May 11.
• Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2006
• Primary Completion (Actual): September 22, 2014
• Study Completion (Actual): September 22, 2014

Study Registration Dates

• First Submitted: October 16, 2007
• First Submitted That Met QC Criteria: October 16, 2007
• First Posted (Estimate): October 17, 2007

Study Record Updates

• Last Update Posted (Actual): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Pertuzumab
• Other Study ID Numbers: WO20697