Health Canada approves Perjeta for use pre-surgery in patients with aggressive early breast cancer[1]

MISSISSAUGA, ON, March 16, 2021 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) is pleased to announce today that Health Canada has granted market authorization to Perjeta^® (pertuzumab for injection) as a neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node positive). Perjeta, in combination with trastuzumab and chemotherapy was previously authorized in 2018 as an adjuvant treatment of patients with HER2-positive early breast cancer with lymph node positive and/or hormone receptor negative disease.³ In 2013, Perjeta was approved for the treatment of HER2-positive metastatic breast cancer.⁴

“This new approval is very important for patients with early aggressive breast cancer since we know how critical it is to give the best neoadjuvant therapy,” says Dr. Karen Gelmon, Professor of Medicine, University of British Columbia, BC Cancer. “The addition of Perjeta to early treatment can lead to longer term survival without adding toxicity, and we already have good experience using Perjeta in other settings; this is great news for the Canadian breast cancer community.”

Treating people with breast cancer early, before the cancer has spread, may improve the chance of preventing the disease from returning.⁵ Neoadjuvant treatment is given before surgery and is aimed at reducing tumour size so it is easier to surgically remove. Pathologic complete response (pCR) refers to the absence of invasive cancer in the breast and/or lymph nodes and achieving pCR following neoadjuvant chemotherapy is a desirable outcome, frequently, as it enables optimization of subsequent treatment decisions, leading to improved survival.⁶

In 2020, more than 27,000 women were diagnosed with breast cancer in 2020.⁷ Approximately 20 per cent of women diagnosed with breast cancer in Canada will have HER2-positive disease, an aggressive form of the disease that is more likely to spread and recur.^8,9

“This approval recognizes the importance of better, smarter treatment pathways that offer the best long-term results for people with breast cancer,” says MJ DeCoteau, Executive Director of Rethink Breast Cancer. “A breast cancer diagnosis is devastating. And when a young woman gets breast cancer, it can be more aggressive and with an increased risk of recurrence. But regardless of the age or stage of the breast cancer, what all patients want is the same – the best possible care that will lead to the best possible outcome.”

“Recurrence is a key concern for many breast cancer patients,” states Cathy Ammendolea, Chair of the Board of Directors of the Canadian Breast Cancer Network. “Providing access to effective therapies in the earliest setting is critical for reducing the chances of a patient’s disease returning.”

The Health Canada approval is based primarily on data from the neoadjuvant Phase II NeoSphere study, which showed that nearly 40 per cent of people receiving the combination of Perjeta, Herceptin, and chemotherapy achieved pCR in the affected breast and local lymph nodes compared to 21.5 per cent of people who received Herceptin and taxane chemotherapy alone.^10,11 The approval was also supported by data from the Phase II neoadjuvant TRYPHAENA and BERENICE studies, in which pCR rates ranging from 54.7 per cent to 63.6 per cent were achieved across the Perjeta-containing study arms.¹² Long-term safety results from the Phase III CLEOPATRA trial in people with previously untreated HER2-positive advanced breast cancer also supported the approval.¹³ Data from the ongoing Phase III APHINITY study in the adjuvant (post-surgery) setting will provide additional insights into the broader role of Perjeta in the treatment of HER2-positive eBC.¹⁴

Follow-up data from the NeoSphere trial suggested that people who received the Perjeta regimen prior to surgery were 31 per cent less likely to experience disease worsening, recurrence or death (PFS HR=0.69; 95 per cent CI, 0.34–1.40) compared to those who received Herceptin and chemotherapy.¹⁵ People treated with the Perjeta regimen were also 40 per cent less likely to experience disease recurrence or death (DFS HR=0.60; 95% CI, 0.28–1.27). These new data suggest that the pCR benefit seen with the Perjeta regimen may translate into longer-term improvements in patient outcomes. Perjeta was approved as neoadjuvant treatment for people with HER2-positive eBC in the U.S. in 2013, and in Europe since 2015.

This new neoadjuvant indication for Perjeta is for use prior to surgery in combination with trastuzumab and taxane-based chemotherapy in people with HER2-positive, locally advanced, inflammatory, or early stage (tumour is greater than two centimeters in diameter or node positive) breast cancer. Perjeta should be used as part of a complete treatment regimen for early stage breast cancer. This use of Perjeta is based on an improvement in the percentage of people who had no evidence of cancer in the breast at the time of surgery. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival.

The safety of Perjeta administered for greater than six cycles for early stage breast cancer has not been established. Please see Perjeta full Prescribing Information including Most Serious Side Effects for additional Important Safety Information at www.rochecanada.com.

“Perjeta’s approval in the neoadjuvant setting is a critical step forward for the treatment of breast cancer and Canadians have been waiting a long time for this option,” says Laura Shields, Oncology Leader at Roche Canada. “Roche remains committed and steadfast in our promise to be a partner to patients and their healthcare teams to bring forward innovative solutions that improve cancer care and patient outcomes.”

About the NeoSphere trial
The NeoSphere trial¹⁶ (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomized, multicentre, international Phase II study in 417 people with newly diagnosed HER2-positive, operable, locally advanced, or inflammatory eBC. Participants were randomized to one of four study arms and received four cycles (12 weeks) of neoadjuvant treatment followed by surgery and a year of adjuvant treatment with Herceptin plus chemotherapy. The primary endpoint was pCR in the breast. Secondary endpoints included clinical response, time to clinical response, safety profile, PFS, DFS, breast-conserving surgery rate and biomarker assessment. Study data showed the following:

• The Perjeta regimen was not associated with a significant increase in adverse events (AEs), compared to Herceptin and chemotherapy alone
• The most common severe (Grade 3 or higher) AEs for the Perjeta regimen were neutropenia (decrease in a certain type of white blood cell, 44.9 per cent), febrile neutropenia (fever associated with decrease in a certain type of white blood cell, 8.4 per cent), leukopenia (decrease in overall white blood cells, 4.7 per cent) and diarrhoea (5.6 per cent)

About the TRYPHAENA trial
The TRYPHAENA trial¹⁷ (ToleRabilitY of Pertuzumab, Herceptin and AnthracyclinEs in NeoAdjuvant breast cancer) is a randomised, multicentre Phase II study that was conducted in 225 people with HER2-positive, operable, locally advanced or inflammatory eBC with tumours greater than two centimetres. Participants were randomized to one of three neoadjuvant Perjeta regimens. The primary endpoint was cardiac safety. Secondary endpoints included pCR, clinical response, breast-conserving surgery rate, DFS, PFS, overall survival (OS) and biomarker assessment. Study data showed the following:

• The study was not powered to compare the three study arms. The rates of total pCR in the breast and local lymph nodes in the three arms were as follows:
  • pCR of 56.2 per cent for Perjeta, Herceptin and anthracycline-based chemotherapy, followed by Perjeta, Herceptin and chemotherapy
  • pCR of 54.7 per cent for anthracycline-based chemotherapy, followed by Perjeta, Herceptin and chemotherapy
  • pCR of 63.6 per cent for the anthracycline-free arm (Perjeta, Herceptin, chemotherapy and carboplatin chemotherapy)
• No new or unexpected cardiac AEs, or other AEs, were observed in any of the study arms. AEs observed were consistent with those seen in previous studies of Perjeta, Herceptin and chemotherapy, either in combination or alone.
• The most common severe (Grade 3 or higher) AEs in any of the three study arms were:
  • In the concurrent arm: neutropenia (47.2 per cent), leukopenia (19.4%) and febrile neutropenia (18.1 per cent)
  • In the sequential arm: neutropenia (42.7 per cent), leukopenia (12.0 per cent), febrile neutropenia (9.3 per cent), diarrhoea (5.3 per cent) and left ventricular dysfunction (4.0 per cent)
  • In the anthracycline-free arm: neutropenia (46.1 per cent), febrile neutropenia (17.1 per cent), anaemia (decrease in red blood cells, 17.1 per cent); the AEs of diarrhoea, leukopenia, anaemia and thrombocytopenia (decrease in platelets) all had an incidence of 11.8 per cent.

About the BERENICE trial
The BERENICE trial¹⁸ is a non-randomised, multicentre, Phase II study that was conducted in 401 patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer with tumours greater than 2 cm or node-positive. The primary endpoint was cardiac safety. Secondary endpoints were overall safety, pCR, clinical response, event-free survival, invasive disease-free survival, and OS. Study data showed the following:

• The study was not designed to compare between treatment cohorts. The rates of total pCR in the breast and lymph nodes in the two treatment cohorts were:
  • pCR of 61.8 per cent for dose-dense anthracycline-based chemotherapy, followed by Perjeta, Herceptin and taxane-chemotherapy
  • pCR of 60.7 per cent for three-weekly anthracycline-based chemotherapy, followed by Perjeta, Herceptin and taxane-chemotherapy
• No new or unexpected cardiac AEs, or other AEs, were observed in either study cohort. AEs observed were consistent with those seen in previous studies of Perjeta, Herceptin and chemotherapy, either in combination or alone
• The most common severe (Grade 3 or higher) AEs in the treatment cohorts were:
  • In the dose-dense anthracycline-containing regimen: neutropenia (12.1 per cent) and febrile neutropenia (7.0 per cent)
  • In the three-weekly anthracycline-based chemotherapy regimen: febrile neutropenia (17.2 per cent), diarrhoea (10.1 per cent), and neutropenia (8.6 per cent)

About Breast Cancer
Breast cancer is the second leading cause of death in Canadian women. In 2020, an estimated 27,400 women were diagnosed and 5,100 died.¹⁹ However, the majority of breast cancer in Canada is diagnosed at an early stage when treatment has a curative intent, and the goal is to prevent recurrence.^20,21,22 Breast cancer mostly occurs in women between 50 and 69 years of age, and the risk of being diagnosed with breast cancer increases with age.²³

About Perjeta
Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerising’) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumour growth and survival.²⁴ The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumour cell growth and survival.²⁵

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 innovations in HER2-positive breast cancer. 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.

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REFERENCES

SOURCE Roche Canada