Roche announced that the European Commission (EC) has approved the use of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) and chemotherapy for the neoadjuvant treatment (use before surgery) of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence. The Perjeta regimen is the first neoadjuvant breast cancer treatment approved by the EC based on pCR data.

Every year in Europe nearly 100,000 people are diagnosed with HER2-positive breast cancer, an aggressive type of the disease that is more likely to progress than HER2-negative cancer. Treating people with breast cancer early, before the cancer has spread, may improve the chance of preventing the disease from returning. Neoadjuvant treatment is given before surgery and is aimed at reducing tumour size so it is easier to surgically remove. pCR is achieved when there is no tumour tissue detectable at the time of surgery in the affected breast or in the affected breast and local lymph nodes. It is a common measure of neoadjuvant treatment effect in breast cancer and it can be assessed more quickly than traditional endpoints in eBC.

“Today’s approval is a significant milestone in the neoadjuvant treatment of HER2-positive early breast cancer, bringing Perjeta to patients years earlier than typical adjuvant treatment,” said Sandra Horning, M.D., Roche’s chief medical officer and head, global product development. “We are committed to making the Perjeta regimen available to appropriate patients in the EU as early as possible.”

The EC approval is based primarily on data from the neoadjuvant phase II NeoSphere study, which showed that nearly 40% of people receiving the combination of Perjeta, Herceptin and chemotherapy achieved pCR in the affected breast and local lymph nodes compared to 21.5% of people who received Herceptin and taxane chemotherapy alone. The approval was also supported by data from the phase II neoadjuvant TRYPHAENA study, in which pCR rates ranging from 54.7% to 63.6% were achieved across the three Perjeta-containing study arms. Long-term safety results from the phase III CLEOPATRA trial in people with previously untreated HER2-positive advanced breast cancer also supported the approval. 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.

Follow-up data from the NeoSphere trial were presented last month at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO). These data suggested that people who received the Perjeta regimen prior to surgery were 31% less likely to experience disease worsening, recurrence or death (PFS HR=0.69; 95% CI, 0.34–1.40) compared to those who received Herceptin and chemotherapy. People treated with the Perjeta regimen were also 40% 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 is already approved as neoadjuvant treatment for people with HER2-positive eBC in the US and 21 other countries.

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. Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. 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 blockade of HER signalling pathways, thus preventing tumour cell growth and survival.

The NeoSphere trial (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomised, multicentre, international Phase II study in 417 people with newly diagnosed HER2-positive, operable, locally advanced, or inflammatory eBC. Participants were randomised 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. Secondary endpoints included clinical response, time to clinical response, safety profile, PFS, DFS, breast-conserving surgery rate and biomarker assessment.

The TRYPHAENA trial (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 randomised 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.

Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin, Perjeta and Kadcyla. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 20% of patients. Over the past 15 years, the outlook for people with HER2-positive disease has improved to the extent that those with this form of the disease treated with these innovative medicines now typically experience better outcomes than people with less aggressive HER2-negative disease.

Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, saving time from the outset by identifying patients who will likely benefit from these medicines at the onset of their disease.