EXPERIENCE OF USING PERTUZUMAB IN ANTICANCER THERAPY FOR HER2-POSITIVE BREAST CANCER

 Background. Breast cancer is one of the most common malignancies and one of the leading causes of cancer deaths among women in the Russian Federation. The prognosis of the disease is largely determined by the
biological subtype of the tumor. Her2-positive breast cancer is characterized by an aggressive course and unfavorable prognosis. The use of pertuzumab, a recombinant humanized monoclonal antibody to the human epidermal growth factor receptor 2, significantly improved immediate and long-term treatment outcomes.

The aim of the study was to evaluate treatment outcomes in patients with Her2-positive molecular subtype of breast cancer receiving chemotherapy combined with a dual anti-Her2 blockade, and to assess the intensity
and incidence of side effects.

Material and methods. Between 2015 and 2018, 37 patients with Her2-positive breast cancer received chemotherapy combined with a dual anti-HER2 blockade (docetaxel 75 mg/m2 i/v on day 1 + trastuzumab 6 mg/kg (loading dose 8 mg/kg) i/v on day 1 + pertuzumab 420 mg (loading dose 840 mg) i/v on day 1 once every 3 weeks). The mean age of the patients was 45.6 ± 11.6 years.

Results. Neoadjuvant pertuzumab in combination with trastuzumab and docetaxel resulted in pathological complete response in 12 % of patients and pathological partial response in 36 % of patients. Among patients who received the above neoadjuvant therapy regimen, disease progression was observed in 4 % of patients. The most common side effects were weakness and fatigue (5.4 % of cases) and grade I–II leukopenia (5.4 %).

Conclusion. The study demonstrated the efficacy of antitumor therapy with pertuzumab in combination with trastuzumab and docetaxel as well as the absence of severe side effects associated with this treatment regimen in patients with Her2-positive breast cancer. 

1. Kolyadina I.V., Poddubnaya I.V., Frank G.A., Komov D.V., Karseladze A.I., Ermilova V.D., Vishnevskaya Y.V. Heterogenety of stage I breast cancer: biological and prognostic value. Malignant tumours. 2015; 1: 35–45. (in Russian). doi: 10.18027/2224-5057-2015-1-31-40.

2. Kit O.I.. Shatova Yu.S.. Novikova I.A., Vladimirova L.Yu., Ulianova E.P., Komova E.A., Kechedzhiyeva E.E. P53 and BCL2 expression in different breast cancer subtypes. Fundamental Research. 2014; 10: 85–88. (in Russian).

3. Poddubnaya I.V., Frank G.A., Yagudina R.I., Koroleva N.I., Zavalishina L.E. The results of epidemiological screening program of HER2 status in patients with breast cancer in the federal districts of the Russian Federation in 2015. Modern Oncology. 2016; 3(18): 19–26. (in Russian).

4. Plotnikova B.E., Nepomnyashchaya E.M., Grigorov C.V. Risk factors for brain metastases in breast cancer. Scientific Statements. Medicine Series. Pharmacy. 2013; 11(154) (22): 84–89. (in Russian).

5. Rossiyskoye obshchestvo klinicheskoy onkologii (RUSSCO). Practical recommendations for the medical treatment of invasive breast cancer. 2018; 113–144. (in Russian).

6. Kim M.M., Allen P., Gonzalez-Angulo A.M., Woodward W.A., MericBernstam F., Buzdar A.U., Hunt K.K., Kuerer H.M., Litton J.K., Hortobagyi G.N., Buchholz T.A., Mittendorf E.A. Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer. Ann Oncol. 2013 Aug; 24(8): 1999–2004. doi: 10.1093/annonc/mdt131.

7. Nagayama A., Hayashida T., Jinno H., Takahashi M., Seki T., Matsumoto A., Murata T., Ashrafian H., Athanasiou T., Okabayashi K., Kitagawa Y. Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis. J Natl Cancer Inst. 2014 Sep 15; 106(9): dju203. doi: 10.1093/jnci/dju203.

8. Schneeweiss A., Chia S., Hickish T., Harvey V., Eniu A., Hegg R., Tausch C., Seo J.H., Tsai Y.F., Ratnayake J., McNally V., Ross G., Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013; 24(9): 2278–84. doi: 10.1093/annonc/mdt182.

9. Gianni L., Pienkowski T., Im Y.H., Roman L., Tseng L.M., Liu M.C., Lluch A., Staroslawska E., de la Haba-Rodriguez J., Im S.A., Pedrini J.L., 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.

10. Gianni L., Pienkowski T., Im Y.-H. Five-year analysis of the phase II NeoSphere trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). J Clin Oncol. 2015; 33(15_suppl): 505. doi: 10.1200/jco.2015.33.15_suppl.505.

11. Perez E.A., Romond E.H., Suman V.J., Jeong J.H., Sledge G., Geyer C.E.Jr., Martino S., Rastogi P., Gralow J., Swain S.M., Winer E.P., Colon-Otero G., Davidson N.E., Mamounas E., Zujewski J.A., Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20; 32(33): 3744–52. doi: 10.1200/JCO.2014.55.5730.

12. Cameron D., Piccart-Gebhart M.J., Gelber R.D., Procter M., Goldhirsch A., de Azambuja E., Castro G.Jr., Untch M., Smith I., Gianni L., Baselga J., Al-Sakaff N., Lauer S., McFadden E., Leyland-Jones B., Bell R., Dowsett M., Jackisch C.; Herceptin Adjuvant (HERA) Trial Study Team. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25; 389(10075): 1195–1205. doi: 10.1016/S0140-6736(16)32616-2.

13. Curigliano G., Burstein H.J., Winer E.P., Gnant M., Dubsky P., Loibl S., Colleoni M., Regan M.M., Piccart-Gebhart M., Senn H.J., Thürlimann B.; St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017, André F., Baselga J., Bergh J., Bonnefoi H., Brucker S.Y., Cardoso F., Carey L., Ciruelos E., Cuzick J., Denkert C., Di Leo A., Ejlertsen B., Francis P., Galimberti V., Garber J., Gulluoglu B., Goodwin P., Harbeck N., Hayes D.F., Huang C.S., Huober J., Hussein K., Jassem J., Jiang Z., Karlsson P., Morrow M., Orecchia R., Osborne K.C., Pagani O., Partridge A.H., Pritchard K., Ro J., Rutgers E.J.T., Sedlmayer F., Semiglazov V., Shao Z., Smith I., Toi M., Tutt A., Viale G., Watanabe T., Whelan T.J., Xu B. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017 Aug 1; 28(8): 1700–1712. doi: 10.1093/annonc/mdx308.

14. Swain S.M., Miles D., Kim S.B., Im Y.H., Im S.A., Semiglazov V., Ciruelos E., Schneeweiss A., Loi S., Monturus E., Clark E., Knott A., Restuccia E., Benyunes M.C., Cortés J.; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr; 21(4): 519–530. doi: 10.1016/S1470-2045(19)30863-0.

15. Swain S.M., Baselga J., Kim S.B., Ro J., Semiglazov V., Campone M., Ciruelos E., Ferrero J.M., Schneeweiss A., Heeson S., Clark E., Ross G., Benyunes M.C., Cortés J.; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19; 372(8): 724–34. doi: 10.1056/NEJMoa1413513.