Effectiveness of the trastuzumab-pertuzumab dual block in neoadjuvance of HER2 positive breast cancer

Objectives: The combination of trastuzumab and chemotherapy has been the standard neoadjuvant treatment for HER2 positive stages IIA–IIIC breast cancer. However, recent clinical trials support the neoadjuvant use of pertuzumab combined with trastuzumab in conjunction with chemotherapy to improve pathological complete response (pCR) rates. Our main objective was to determine whether the trastuzumab-pertuzumab dual blockade in neoadjuvant HER2-positive breast cancer patients achieves higher rates of pCR relative to patients where only trastuzumab was used. Methods: This was a prospective cohort study in patients at San Pedro’s Hospital in Logroño (Spain) with HER2 positive breast cancer who were candidates for neoadjuvant therapy. 39 patients received dual block treatment and were compared with a non-concurrent (retrospective) control group of 39 patients receiving single block treatment. Results: According to the logit model, the coefficient that relates the probability that the pathological response is complete in the case of dual blockade was positive (2.272) and significant at 1% (p-value less than 0.01). The correlation coefficient between radiological and pathological response was 0.87 when we consider dual block treatment. Mucositis was the most frequent adverse effect (29.49% of the sample). There were 3 cardiac events in the single block group and none in the dual block group. Conclusions: The pCR was greater in the dual block group than in the single block group (69.23% versus 25.64%). There was a greater correlation between radiological and pathological response in dual blockade patients. Safety profile was similar in both groups.

Breast neoplasms; Trastuzumab; Pertuzumab; Pathological complete response (pCR); HER-2 positive

[1] SEOM: Las Cifras Del Cáncer En España. 2018. Avaliable at: https://seom.org/seomcms/images/stories/recursos/Las_Cif ras_del_cancer_en_Espana2018.pdf (Accessed: 10 October 2020).

[2] Ayala de la Peña F, Andrés R, Garcia-Sáenz JA, Manso L, Margelí M, Dalmau E, et al. SEOM clinical guidelines in early stage breast cancer (2018). Clinical & Translational Oncology. 2018; 21: 18–30.

[3] Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010; 375: 377–384.

[4] Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, et al. Abstract P4-21-02: Pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: Efficacy analysis of a phase II cardiac safety study (TRYPHAENA). Cancer Research. 2017; 77: P4-21-02.

[5] Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang C, Thompson AM, et al. Pathologic complete response (pCR) rates after neoadjuvant trastuzumab emtansine (T-DM1 [K]) + pertuzumab (P) vs docetaxel + carboplatin + trastuzumab + P (TCHP) treatment in patients with her2-positive (her2+) early breast cancer (EBC) (KRISTINE). Journal of Clinical Oncology. 2016; 34: 500.

[6] Gianni L, Pienkowski T, Im Y, Roman L, Tseng L, Liu M, et al. 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 Oncology. 2012; 13: 25–32.

[7] Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoad-juvant chemotherapy for early breast cancer (GeparSepto—GBG 69): a randomised, phase 3 trial. Lancet Oncology. 2016; 17: 345–356.

[8] Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, et al. Her2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage her2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncology. 2017; 18: 545–554.

[9] Parekh T, Dodwell D, Sharma N, Shaaban AM. Radiological and Pathological Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer: a Brief Literature Review. Pathobiology. 2015; 82: 124–132.

[10] Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003; 12: 320–327.

[11] Dialani V, Chadashvili T, Slanetz PJ. Role of imaging in neoadjuvant therapy for breast cancer. Annals of Surgical Oncology. 2015; 22: 1416–1424.

[12] Wittekind C, Hutter R, Greene FL, Klimpfinger M, Sobin LH. Union for International Cancer Control (UICC). TNM Atlas. 5th edn. NY: Springer. 2005.

[13] Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. Journal of the National Cancer Institute. 2005; 97: 188–194.

[14] Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014; 384: 164–172.

[15] Gavilá J, Oliveira M, Pascual T, Perez-Garcia J, Gonzàlez X, Canes J, et al. Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial. BMC Medicine. 2019; 17: 8.

[16] Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero J, Verrill M, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with her2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Annals of Oncology. 2018; 29: 646–653.

[17] González-Santiago S, Saura C, Ciruelos E, Alonso JL, de la Morena P, Santisteban Eslava M, et al. Real-world effectiveness of dual her2 blockade with pertuzumab and trastuzumab for neoadjuvant treatment of her2-positive early breast cancer (the NEOPETRA Study). Breast Cancer Research and Treatment. 2020; 184: 469–479.

[18] U.S. Department of Health and Human Services. National Institutes of Health (NIH). National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. 2010. Available at: https://ctep.cancer.gov/protocoldevelopmen t/electronic_applications/docs/CTCAE_4.03.xlsx (Accessed: 14 June 2010).