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

Summary

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).

Timeline

Start

2011-11-08

Primary completion

2016-12-19

Completion

2024-11-28

Outcome

Met primary endpoint

registry analysis (superiority test); Pertuzumab + Trastuzumab + Chemotherapy vs Placebo + Trastuzumab + Chemotherapy; p = 0.0446; Hazard Ratio (HR) 0.81 (95% CI 0.66 to 1.00); NCT01358877 ↗

release “The phase III Aphinity study with Roche’s Perjeta regimen met its primary endpoint.” roche.com ↗

release “APHINITY Study Shows Genentech’s Perjeta-Based Regimen Reduced the Risk of Invasive Cancer Returning Compared to Herceptin and Chemotherapy in HER2-Positive Early Breast Cancer” gene.com ↗

release “Primary endpoint: invasive disease-free survival (iDFS) HR=0.81; 95% CI 0.66-1.00, p=0.045” gene.com ↗

release “APHINITY study, the combination of Perjeta, Herceptin and chemotherapy significantly reduced the risk of invasive breast cancer recurrence or death” roche.com ↗

release “At six years, 90.6% of patients in the Perjeta arm have not seen their breast cancer return, compared to 87.8% in the placebo arm” roche.com ↗

release “The Perjeta-based regimen continued to reduce the risk of breast cancer recurrence or death versus Herceptin, chemotherapy and placebo, by 23%” roche.com ↗

release “The previously reported invasive disease-free survival (primary endpoint) benefit was maintained (HR=0.79, 95% CI: 0.68-0.92), strengthening results from earlier APHINITY analyses.” gene.com ↗

Publications

• Agostinetto 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 Sub-analysis of the APHINITY trial. J Natl Cancer Inst. 2026 Apr 3:djag095. doi: 10.1093/jnci/djag095. Online ahead of print.
• Loibl 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.
• de 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.
• Lambertini 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.
• Gelber 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.
• Bines J, Clark E, Barton C, Restuccia E, Procter M, Sonnenblick A, Fumagalli D, Parlier D, Arahmani A, Baselga J, Viale G, Reaby LL, Frank E, Gelber RD, Piccart M, Jackisch C, Petersen JA. Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer. Br J Cancer. 2021 Jul;125(1):38-47. doi: 10.1038/s41416-021-01323-y. Epub 2021 Apr 7.
• Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pienkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. doi: 10.1200/JCO.20.01204. Epub 2021 Feb 4.
• Bines J, Procter M, Restuccia E, Viale G, Zardavas D, Suter T, Arahmani A, Van Dooren V, Baselga J, Clark E, Eng-Wong J, Gelber RD, Piccart M, Mobus V, de Azambuja E; APHINITY Steering Committee and Investigators. Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. Clin Breast Cancer. 2020 Apr;20(2):174-181.e3. doi: 10.1016/j.clbc.2019.06.016. Epub 2019 Sep 5.
• Luo Y, Li W, Jiang Z, Zhang Q, Wang L, Mao Y, Tjan-Heijnen VCG, Im SA, McConnell R, Bejarano S, Fumagalli D, Bines J, Wang B, Garg A, Kirschbrown WP, Xu B. Pharmacokinetics of pertuzumab administered concurrently with trastuzumab in Chinese patients with HER2-positive early breast cancer. Anticancer Drugs. 2019 Sep;30(8):866-872. doi: 10.1097/CAD.0000000000000808.
• Kirschbrown WP, Kagedal M, Wang B, Lindbom L, Knott A, Mack R, Monemi S, Nijem I, Girish S, Freeman C, Fumagalli D, McConnell R, Jerusalem G, Twelves C, Baselga J, von Minckwitz G, Bines J, Garg A. Pharmacokinetic and exploratory exposure-response analysis of pertuzumab in patients with operable HER2-positive early breast cancer in the APHINITY study. Cancer Chemother Pharmacol. 2019 Jun;83(6):1147-1158. doi: 10.1007/s00280-019-03826-1. Epub 2019 Apr 11.
• von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. doi: 10.1056/NEJMoa1703643. Epub 2017 Jun 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pertuzumab	Monoclonal antibody	420 mg	Intravenous
Background	Carboplatin	Small molecule	900 mg	Intravenous
Background	Cyclophosphamide	Other / unclassified	500 mg/m2	Intravenous
Background	Cyclophosphamide	Other / unclassified	600 mg/m2	Intravenous
Background	Docetaxel	Small molecule	75 mg/m2	Intravenous
Background	Docetaxel	Small molecule	100 mg/m2	Intravenous
Background	Doxorubicin	Other / unclassified	50 mg/m2	Intravenous
Background	Doxorubicin	Other / unclassified	60 mg/m2	Intravenous
Background	Epirubicin	Small molecule	90 mg/m2	Intravenous
Background	Epirubicin	Small molecule	120 mg/m2	Intravenous
Background	Paclitaxel	Small molecule	80 mg/m2	Intravenous
Background	Trastuzumab	Monoclonal antibody	6 mg/kg	Intravenous
Background	fluorouracil	Small molecule	500 mg/m2	Intravenous
Background	fluorouracil	Small molecule	600 mg/m2	Intravenous

Indications