Clinical trial · Interventional
A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer
A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
NCT01358877CI-TRIAL-00098085APHINITYcompletedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. This study will be carried out in collaboration with the Breast International Group (BIG).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (10)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-Fluorouracil | Drug | Fluorouracil | ALIAS |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Docetaxel | Drug | Docetaxel | ALIAS |
| Doxorubicin | Drug | Doxorubicin | ALIAS |
| Epirubicin | Drug | Epirubicin | ALIAS |
| Paclitaxel | Drug | Paclitaxel | ALIAS |
| Pertuzumab | Drug | Pertuzumab | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Pertuzumab + Trastuzumab + Chemotherapy
- description
- Participants will receive pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m\^2 + epirubicin 90-120 mg/m\^2 or doxorubicin 50 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m\^2 for 3 cycles, 75 mg/m\^2 in first cycle and 100 mg/m\^2 in subsequent cycles, or 75 mg/m\^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m\^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m\^2 or epirubicin 90-120 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m\^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).
- interventionNames
- Drug: 5-Fluorouracil
- Drug: Carboplatin
- Drug: Cyclophosphamide
- Drug: Docetaxel
- Drug: Doxorubicin
- Drug: Epirubicin
- Drug: Paclitaxel
- Drug: Pertuzumab
- Drug: Trastuzumab
- type
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\</=) 1 * Known hormone receptor status (estrogen receptor and progesterone receptor) * The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first * Baseline left ventricular ejection fraction (LVEF) greater than or equal to (\>/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan * Confirmed HER2 positive status * Completion of all necessary baseline laboratory and radiologic investigations prior to randomization * Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug Exclusion Criteria: * History of any prior (ipsi- and/or contralateral) invasive breast cancer * History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin * Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer * Any node-negative tumor * Any previous systemic chemotherapy for cancer or radiotherapy for cancer * Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer * Concurrent anti-cancer treatment in another investigational trial * Serious cardiac or cardiovascular disease or condition * Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness * Abnormal laboratory tests immediately prior to randomization * Pregnant or lactating women * Sensitivity to any of the study medications or any of the ingredients or excipients of these medications
References
Publications (11)
- DERIVEDAgostinetto E, Gentile G, Samy F, Di Cosimo S, Aftimos P, Ponde N, Eiger D, Lambertini M, Cameron D, Kiermaier A, Bailey A, Viale G, Loi S, Piccart M, de Azambuja E. The benefit of adjuvant pertuzumab and trastuzumab according to estrogen receptor and HER2 expression: a subanalysis of the APHINITY trial. J Natl Cancer Inst. 2026 Aug 1;118(8):1504-1513. doi: 10.1093/jnci/djag095. PMID 41934626
- DERIVEDLoibl S, Jassem J, Sonnenblick A, Parlier D, Winer E, Bergh J, Gelber RD, Restuccia E, Im YH, Huang CS, Dalenc F, Calvo I, Procter M, Caballero C, Clark E, Raimbault A, McConnell R, Monturus E, de Azambuja E, Gomez HL, Bliss J, Viale G, Bines J, Piccart M; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update. J Clin Oncol. 2024 Nov;42(31):3643-3651. doi: 10.1200/JCO.23.02505. Epub 2024 Sep 11. PMID 39259927
- DERIVEDde Azambuja E, Agostinetto E, Procter M, Eiger D, Ponde N, Guillaume S, Parlier D, Lambertini M, Desmet A, Caballero C, Aguila C, Jerusalem G, Walshe JM, Frank E, Bines J, Loibl S, Piccart-Gebhart M, Ewer MS, Dent S, Plummer C, Suter T; APHINITY Steering Committee and Investigators. Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial. ESMO Open. 2023 Feb;8(1):100772. doi: 10.1016/j.esmoop.2022.100772. Epub 2023 Jan 19. PMID 36681013
- DERIVEDLambertini M, Fielding S, Loibl S, Janni W, Clark E, Franzoi MA, Fumagalli D, Caballero C, Arecco L, Salomoni S, Ponde NF, Poggio F, Kim HJ, Villarreal-Garza C, Pagani O, Paluch-Shimon S, Ballestrero A, Del Mastro L, Piccart M, Bines J, Partridge AH, de Azambuja E. Impact of Age on Clinical Outcomes and Efficacy of Adjuvant Dual Anti-HER2 Targeted Therapy. J Natl Cancer Inst. 2022 Aug 8;114(8):1117-1126. doi: 10.1093/jnci/djac096. PMID 35512402
- DERIVEDGelber RD, Wang XV, Cole BF, Cameron D, Cardoso F, Tjan-Heijnen V, Krop I, Loi S, Salgado R, Kiermaier A, Frank E, Fumagalli D, Caballero C, de Azambuja E, Procter M, Clark E, Restuccia E, Heeson S, Bines J, Loibl S, Piccart-Gebhart M; APHINITY Steering Committee and Investigators. Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial. Eur J Cancer. 2022 May;166:219-228. doi: 10.1016/j.ejca.2022.01.031. Epub 2022 Mar 18.