DUAL HER2 BLOCKADE WITH TRASTUZUMAB AND PERTUZAMB IN HER2- POSITIVE BREAST CANCER: SINGLE CENTER REAL WORLD DATA
Agents targeting the human epidermal growth factor receptor 2 (HER2) have improved outcomes of advanced HER2-positive breast cancer with durable responses. We evaluated therapy with trastuzumab and pertuzumab in early and metastatic HER2-positive breast cancer patients. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the single center setting. We retrospectively identifed patients on adjuvant and frst-line anti-HER2 therapy at The University Clinic of Radiotherapy and Oncology Skopje for at least 1 year from 2019 to 2020. Demographics, treatments and adverse events were recorded. The combination of pertuzumab–trastuzumab has established efficacy in patients with HER2‐positive advanced/metastatic breast cancer. Management of treatment related side‐effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such may require particular management strategies.The roles of trastuzumab and pertuzumab are now very well established in the frst-line setting; identifying predictors of long-term response to these would be important in selecting which patients might beneft from entry into future clinical trials assessing the long-term beneft of these newer agents in addition.
Keywords: Breast cancer, HER2 positive, Trastuzumab, Pertuzumab.
2.Smith IE. Efficacy and safety of Herceptin in women with metastatic breast cancer: results from pivotal clinical studies. Anticancer Drugs. 2001;12 Suppl 4:S3-10.
3.O’Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. Oncologist. 2005;10 Suppl 3:20-29.
4.Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719-726.
5.Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17(9):2639-2648.
6.Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265-4274.
7.Kaufman B, Mackey JR, Clemens MR, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009;27(33):5529-5537.
8.Baselga J, Cortés J, Kim S-B, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119.
9.Swain SM, Baselga J, Kim S-B, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-734.
10.Giordano SH, Temin S, Kirshner JJ, et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(19):2078-2099.
11.Dang C, Iyengar N, Datko F, et al. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015;33(5):442-447.
12.Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase iii marianne study. J Clin Oncol. 2017;35(2):141-148.
13. Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006;24(18):2786-2792.
14.Bullock K, Blackwell K. Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist. 2008;13(5):515-525.
15.Seidman AD, Fornier MN, Esteva FJ, et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001;19(10):2587-2595.
16.Melosky B. Supportive care treatments for toxicities of anti-egfr and other targeted agents. Curr Oncol. 2012;19(Suppl 1):S59-63.
17.Gibson RJ, Keefe DMK. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer. 2006;14(9):890-900.
18.Benson AB, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004;22(14):2918-2926.
19.Mortimer J, Jung J, Yuan Y, et al. Skin/nail infections with the addition of pertuzumab to trastuzumab-based chemotherapy. Breast Cancer Res Treat. 2014;148(3):563-570.
20. Drucker AM, Wu S, Dang CT, Lacouture ME. Risk of rash with the anti-HER2 dimerization antibody pertuzumab: a meta-analysis. Breast Cancer Res Treat. 2012;135(2):347-354.
21.Jia Y, Lacouture ME, Su X, Wu S. Risk of skin rash associated with erlotinib in cancer patients: a meta-analysis. J Support Oncol. 2009;7(6):211-217.
22.Su X, Lacouture ME, Jia Y, Wu S. Risk of high-grade skin rash in cancer patients treated with cetuximab--an antibody against epidermal growth factor receptor: systemic review and meta-analysis. Oncology. 2009;77(2):124-133.
23.Ocvirk J, Heeger S, McCloud P, Hofheinz R-D. A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a meta-analysis. Radiol Oncol. 2013;47(2):166-175.
24.Malenfant SJ, Eckmann KR, Barnett CM. Pertuzumab: a new targeted therapy for HER2-positive metastatic breast cancer. Pharmacotherapy. 2014;34(1):60-71.
25.Miles D, Baselga J, Amadori D, et al. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (Cleopatra). Breast Cancer Res Treat. 2013;142(1):89-99.
26. Ramakrishna N, Temin S, Chandarlapaty S, et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(19):2100-2108.
27.Swain SM, Baselga J, Miles D, et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014;25(6):1116-1121.
28.Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783-1791.