Health Canada approves Kadcyla® (trastuzumab emtansine) for the treatment of HER2-positive early breast cancer after surgery(1)

Data show patients had a 50% reduction in risk of recurrence compared to treatment with Herceptin® (trastuzumab) after surgery²

MISSISSAUGA, ON, Nov. 28, 2019 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) announced today that Health Canada has approved Kadcyla® (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC) who have residual invasive disease following neoadjuvant (before surgery) taxane and trastuzumab-based treatment.³

HER2-positive breast cancer affects approximately 15-20% of patients⁴ and is a particularly aggressive form of the disease, which is more likely to spread and recur.⁵ Early breast cancer, defined as the presence of a tumour which is confined solely to the breast and has not spread beyond the axillary lymph nodes or to other organs,^6,7 typically involves a combination of treatment approaches such as surgery, radiation, hormonal therapy, chemotherapy and targeted therapies.⁸

There have been significant advancements in screening and treating eBC and physicians approach treatment with a curative intent, aiming to prevent recurrence. Since HER2-positive breast cancer requires chemotherapy with targeted antibody treatment to achieve best curative survival outcomes, this treatment is often provided before surgery (known as neoadjuvant treatment). This allows for significant downstaging of the tumour, providing opportunities to achieve better surgical outcomes and determination of survival outcomes.⁹ The aim is to achieve a pathological complete response with neoadjuvant treatment (meaning no evidence of residual disease within the breast or the lymph nodes), which occurs in 40-60% of patients.^10,11,12 However, in patients who do not experience a pathological complete response after neoadjuvant treatment and surgery, there is a significantly higher risk of disease recurrence. This underlines the importance of having optimal options for patients to treat their disease and reduce the likelihood of it coming back.¹³

"The data supporting the approval of Kadcyla in Canada is meaningful as it shows we have a new treatment option that may reduce the risk of recurrence for some women with this disease – an important step forward in treating HER2-positive eBC," says Dr. Christine Brezden-Masley, Medical Oncologist at Mount Sinai Hospital, Toronto."The goal of treating early breast cancer is to provide people with the best possible outcomes using all possible means, which may involve treatment before and after surgery as a part of a treatment regimen."

Health Canada's approval is based on results of the Phase III KATHERINE study showing Kadcyla significantly reduced the risk of residual invasive breast cancer recurrence or death from any cause (invasive disease-free survival; IDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin as an adjuvant treatment in people with HER2-positive eBC who have residual invasive disease following neoadjuvant taxane and Herceptin-based treatment.¹⁴ At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77% treated with Herceptin, an absolute improvement of 11.3%.¹⁵ People who have residual invasive disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.^16,17

"Fear of the cancer coming back is one of the biggest concerns for women once they complete treatment. Better upfront treatments for women with early breast cancer are critical to preventing metastasis, which sadly continues to take the lives of too many of the women we serve," says MJ DeCoteau, Founder and Executive Director, Rethink Breast Cancer. "These trial findings can help breast cancer patients get the right treatment at the right time—and gives us hope that more women will be cancer-free."

About the KATHERINE study¹⁸
KATHERINE is an international, multi-centre, two-arm, randomized, open-label, Phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological residual invasive disease in the breast and/or axillary lymph nodes following neoadjuvant taxane and Herceptin-based treatment. The primary efficacy endpoint of the study was Invasive Disease Free Survival (IDFS). IDFS was defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumour recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause. Additional endpoints included IDFS including second primary non-breast cancer, disease free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI).

The most common adverse reactions (≥ 10%) with Kadcyla in eBC were fatigue, nausea, increased transaminases (liver enzymes), musculoskeletal pain, hemorrhage, thrombocytopenia (decrease in platelets), headache, peripheral neuropathy (pain in hands and feet), arthralgia (joint pain), epistaxis (nose bleeds), constipation, myalgia (muscle pain), stomatitis (inflammation of mouth and lips), vomiting, insomnia, dry mouth, cough, diarrhea, abdominal pain, pyrexia (fever), urinary tract infection, and anemia.¹⁹

About Kadcyla® (trastuzumab-emtansine)
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.^20,21 It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.²² Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche in Breast Cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with biomarker tests, have contributed to bringing breakthrough innovations in HER2-positive breast cancer. Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta® (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche's HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalized healthcare - a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. 

Founded in 1931, Roche Canada is committed to searching for better ways to prevent, diagnose and treat diseases while making a sustainable contribution to society. The company employs more than 1,200 people across the country through its Pharmaceuticals division in Mississauga, Ontario and Diagnostics, as well as Diabetes Care divisions in Laval, Quebec.

Roche aims to improve patient access to medical innovations by working with all relevant stakeholders. Roche Canada is actively involved in local communities through its charitable giving and partnerships with organizations and healthcare institutions that work together to improve the quality of life of Canadians. For more information, please visit www.RocheCanada.com.

All trade-marks mentioned are the property of their respective owners.

© Copyright 2019; Hoffmann-La Roche Limited

REFERENCES

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^1	Kadcyla Product Monograph; November 2019
^2	Kadcyla Product Monograph; November 2019
^3	Kadcyla Product Monograph; November 2019
^4	Wolff AC, et al. (2013) Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer, J Clin Oncol. 31(31):3997-4013
^5	Canadian Cancer Society. Prognosis and Survival for Breast Cancer. Retrieved from: http://www.cancer.ca/en/cancer-information/cancer-type/breast/prognosis-and-survival/?region=on
^6	World Health Organization. Early Stage Breast Cancer. Retrieved from: https://www.who.int/selection_medicines/committees/expert/20/applications/EarlyStageBreast.pdf?ua=1
^7	National Cancer Institute. Dictionary of Cancer Terms. Early-Stage Breast Cancer. Retrieved from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer
^8	Canadian Cancer Society. Treatments for Breast Cancer. Retrieved from: https://www.cancer.ca/en/cancer-information/cancer-type/breast/treatment/?region=on
^9	Vaidya, J. S. et al. (2018) 'Rethinking neoadjuvant chemotherapy for breast cancer', British Medical Journal, 360: j5913
^10	Schneeweiss A, Chia S, Hickish T, et al. (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer, Ann Oncol. 24(9):2278-84
^11	Gianni L, Pienkowski T, Im YH, et al. (2012) 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. 13(1):25-32
^12	Swain SM, Ewer MS, Viale G, et al. (2018) Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE), Ann Oncol. 29(3): 646-653
^13	Von Minckwitz G, et al. (2018) Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer, N Engl J Med. DOI:10.1056/NEJMoa1814017
^14	Kadcyla Product Monograph; November 2019
^15	Kadcyla Product Monograph; November 2019
^16	Cortazar P, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72
^17	Von Minckwitz G, et al. (2018) Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer, N Engl J Med. DOI:10.1056/NEJMoa1814017
^18	Kadcyla Product Monograph; November 2019
^19	Kadcyla Product Monograph; November 2019
^20	Hurvitz SA, et al. (2013). Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer, J Clin Oncol. 31(9):1157-63
^21	Verma S, et al. (2012) Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer, N Engl J Med. 367(19):1783-91
^22	Junttila TT, et al. (2011) Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer, Breast Cancer Res Treat. 128:347–56

SOURCE Hoffmann-La Roche Limited (Roche Canada)

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