Health Canada grants market authorization for Tecentriq® in combination with bevacizumab,[1] the first immunotherapy combination treatment, for the most common form of liver cancer[2]

Tecentriq in combination with bevacizumab improved overall survival and progression-free survival compared to the previous standard of care^[3]

MISSISSAUGA, ON, Aug. 19, 2020 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) today announced that Health Canada has granted market authorization for Tecentriq (atezolizumab for injection), in combination with bevacizumab, for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who require systemic therapy.^[4]

HCC is one of the fastest rising cancers in Canada with incidence rates almost tripling since the early 1980s.^[5] In 2019, an estimated 3,000 Canadians were diagnosed with liver cancer^[6] and of those, HCC was the most common form.^[7] Liver cancer is often diagnosed at the advanced stage of the disease^[8] resulting in limited treatment options and poor prognosis.^[9],[10] On average, 5-year survival rates are 19%,^[11] which underscores the need for new effective treatment options. The main risk factors for liver cancer are chronic liver disease and cirrhosis caused by viral hepatitis and excessive alcohol intake.^[12]  

The Canadian authorization was granted by Health Canada as a part of Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE) which provides a framework for simultaneous submission and review of oncology products among international partners.^[13] This important initiative gives international regulators the ability to provide patients with cancer, like those with HCC, access to pivotal products sooner.^[14] Simultaneous applications were submitted in Canada, the United States, Australia and Singapore.

The approval of Tecentriq in combination with bevacizumab is likely to change clinical practice for many patients with previously untreated unresectable HCC," said Dr. Jennifer Knox, Staff Medical Oncologist, Princess Margaret Cancer Centre, Toronto. "I'm pleased that for the first time in over a decade I am able to offer patients a new therapy that data indicates can delay progression and improve overall survival in a more meaningful way for my patients."  

This authorization is based on results from the randomized Phase III IMbrave 150 study.^[15] The study showed Tecentriq in combination with bevacizumab reduced the risk of death (overall survival; OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease worsening or death (progression-free survival; PFS) by 41% (HR=0.59; 95% CI: 0.47-0.76; p<0.0001), compared with sorafenib,^[16] the current standard of care for the treatment of HCC in Canada.^[17]

IMbrave150 is the first Phase III cancer immunotherapy study to show an improvement in OS and PFS in people with unresectable HCC compared with sorafenib. This marks the first time in more than a decade that a new treatment showed a significant improvement and a clinical benefit over standard of care for patients with unresectable HCC.^[18]

"Hepatocellular carcinoma is a fast-growing cancer in Canada and one often diagnosed late and is without multiple treatment options," said Jackie Manthorne, President and CEO, Canadian Cancer Survivors Network. "We are pleased to see this combination gain approval in Canada providing new and important treatment options for patients."

About the IMbrave150 study
IMbrave150 is a global Phase III, randomized, multi-center, open-label study, conducted to evaluate the efficacy and safety of Tecentriq in combination with bevacizumab, in patients with unresectable or metastatic HCC, who have not received prior systemic treatment. A total of 501 patients were randomized (2:1) to receive either Tecentriq 1,200 mg and 15 mg/kg of bevacizumab every three weeks administered via IV infusion, or sorafenib 400 mg orally twice per day.^[19]

The co-primary efficacy endpoints as assessed by an independent review facility (IRF) were OS and PFS according to evaluation criteria in solid tumours (RECIST v1.1). At the time of the primary analysis, patients had a median survival follow up time of 8.6 months. The data demonstrated a statistically significant improvement in OS and PFS as assessed by IRF per RECIST v1.1 with Tecentriq in combination with bevacizumab compared to sorafenib. A statistically significant improvement was also observed in confirmed objective response rate (ORR).^[20]

The study findings also demonstrated a 7.6-month delay in median time to deterioration of patient-reported quality of life (a predefined descriptive secondary endpoint) with Tecentriq in combination with bevacizumab compared with sorafenib (11.2 versus 3.6 months; HR=0.63; 95% CI: 0.46–.85).^[21]

The most common adverse reactions (≥10 %) in the IMbrave150 study included: hypertension (29.8%), fatigue (20.4%), pyrexia (17.9%), proteinuria (20.1%), aspartate aminotransferase increased (19.5%), alanine aminotransferase increased (14%), blood bilirubin increased (13.1%), weight decreased (11.2%), platelet count decreased (10.6%), pruritus (19.5%), rash (12.5%), diarrhea (18.8%), constipation (13.4%) , abdominal pain (12.2%), nausea (12.25), vomiting (10%), decreased appetite (17.6%), cough (11.9%), epistaxis (10.3%), infusion related reaction (11.2%).^[22]

About the Tecentriq® (atezolizumab) and bevacizumab combination
There is a strong scientific rationale to support the use of Tecentriq plus bevacizumab in combination. The combination may enhance the ability of the immune system to combat a broad range of cancers. Bevacizumab, in addition to its established anti-angiogenic effects, may further enhance Tecentriq's ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.^[23]

About Tecentriq® (atezolizumab)
Tecentriq is a monoclonal antibody designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells. This blocks the interactions of PD-L1 with other cell-surface receptors which regulate the activation or suppression of T-cells.^[24]

Roche has a development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.^[25]

In Canada, Tecentriq is authorized in combination with chemotherapy (carboplatin and etoposide) for the first-line treatment of adults with extensive-stage small cell lung cancer, as well as in combination with bevacizumab and chemotherapy (paclitaxel and carboplatin) for the first-line treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic non-squamous NSCLC. Tecentriq is also authorized for the treatment of people with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on a therapy for these aberrations prior to receiving Tecentriq. It is also authorized in combination with bevacizumab for the treatment of patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy. In addition, Tecentriq is authorized conditionally and is indicated for the treatment of patients with metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression with 12 months of neoadjuvant or adjuvant treatment with platinum-containing therapy. It is also conditionally authorized in combination with chemotherapy (nab-paclitaxel) for the treatment of adult patients with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have PD-L1 expression ≥ 1%, and who have not received prior chemotherapy for metastatic disease. ^[26]

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 2020; Hoffmann-La Roche Limited

REFERENCES

^[1] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[2] Canadian Liver Foundation. Liver Cancer and Tumours. Available at: https://www.liver.ca/patients-caregivers/liver-diseases/liver-cancer/. [Accessed March 2020].
^[3] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[4] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[5] De P, Dryer D, Otterstatter MC, Semenciw R. Canadian trends in liver cancer: a brief clinical and epidemiologic overview. Curr Oncol. 2013;20(1):e40-3. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557341// [Accessed March 2020].
^[6] Canadian Cancer Society. Liver Cancer Statistics. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/liver/statistics/?region=on [Accessed March 2020].
^[7] Canadian Liver Foundation. Liver Cancer and Tumours. Available at: https://www.liver.ca/patients-caregivers/liver-diseases/liver-cancer/. [Accessed March 2020].
^[8] Canadian Cancer Society. Treatments for liver cancer. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/liver/treatment/?region=qc. [Accessed March 2020].
^[9] Thein HH, Khoo E, Campitelli MA, et al. Trends in relative survival in patients with a diagnosis of hepatocellular carcinoma in Ontario: a population-based retrospective cohort study. CMAJ Open. 2015;3(2):E208-16. Available at: http://cmajopen.ca/content/3/2/E208.full. [Accessed March 2020].
^[10] Canadian Cancer Society. Treatments for liver cancer. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/liver/treatment/?region=qc. [Accessed March 2020].
^[11] Canadian Cancer Society. Survival Statistics for Liver Cancer. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/liver/prognosis-and-survival/survival-statistics/?region=qc. [Accessed March 2020].
^[12] Balogh J, Victor D, Asham EH, et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016;3:41-53. Available at; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063561/. [Accessed March 2020].
^[13] U.S. Food and Drug Administration. Project Orbis. Available at: https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis. [Accessed May 2020].
^[14] Health Canada. International collaboration among Canadian, U.S. and Australian regulators leads to new options for the treatment of cancer. Available at: https://www.canada.ca/en/health-canada/news/2019/12/international-collaboration-among-canadian-us-and-australian-regulators-leads-to-new-options-for-the-treatment-of-cancer.html. [Accessed March 2020].
^[15] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[16] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[17] Canadian Cancer Society. Research in liver cancer. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/liver/research/?region=qc. [Accessed April 2020].
^[18] Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-390. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa0708857 [Accessed May 2020].
^[19] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[20] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[21] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[22] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[23] Reck M, et al. IMpower150 PFS analysis. IMpower150 PFS analysis. Available at: https://www.roche.com/dam/jcr:0f4bded2-f3a7-4b40-a654-3e273ba15161/en/ESMO_IO_IMpower150.pdf. [Accessed May 2020].
^[24] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.
^[25] Roche. How We Work; Pipeline. Available at: https://www.roche.com/research_and_development/who_we_are_how_we_work/pipeline.htm. [Accessed May 2020].
^[26] TECENTRIQ (atezolizumab) Product Monograph; August 7, 2020.

SOURCE Hoffmann-La Roche Limited (Roche Canada)

Bridget Wells, Roche Canada, T: 905-542-5072, E: [email protected]; Sydney Dubin, Proof Inc., T: 416-969-2816, E: [email protected]

Related Links

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