The US Food and Drug Administration (FDA) has accepted Roche’s supplemental Biologics License Application (sBLA) for the use of a Perjeta (pertuzumab) regimen before surgery (neoadjuvant treatment) in people with HER2-positive early-stage breast cancer. The FDA has granted a Priority Review of the application and will make a decision on approval by October 31, 2013.

“The impact of treatment in breast cancer is greatest in the early stage, before the cancer has spread to other parts of the body,” said Hal Barron, MD, Roche’s chief medical officer and head, Global Product Development. “We look forward to working with the FDA to bring this potential option to people with HER2-positive early-stage breast cancer as soon as possible.”

Neoadjuvant therapy is a treatment option given after diagnosis but before surgery for early-stage breast cancer (cancer that has not spread beyond the breast or lymph nodes). Neoadjuvant treatment aims to reduce a tumour’s size so it may be easier to surgically remove, or to allow for breast-conserving surgery. There are currently no FDA-approved neoadjuvant treatments for cancer. A common measure of neoadjuvant treatment effect in breast cancer is pathological complete response (pCR), which means there is no tumour tissue detectable at the time of surgery. Perjeta is already approved in the US and Europe for people with HER2-positive metastatic breast cancer, an advanced form of the disease.

Perjeta is a personalised medicine that targets the HER2 receptor, a protein found in high quantities on the outside of cancer cells in HER2-positive cancers. The combination of Perjeta, Herceptin and docetaxel chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways.

A Priority Review designation is granted to medicines that the FDA believes have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

The application is based primarily on results from NEOSPHERE and TRYPHAENA, two phase II studies of Perjeta in HER2-positive early-stage breast cancer, as well as on longer-term safety data from the phase III CLEOPATRA study of Perjeta in HER2-positive metastatic breast cancer.

The NEOSPHERE study (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomised, multi-centre, international phase II study that was conducted in 417 people with newly diagnosed HER2-positive, locally advanced, inflammatory or early-stage breast cancer. Participants were randomised to four study arms and received four cycles (12 weeks) of neoadjuvant treatment. The primary endpoint was pCR. Secondary endpoints included clinical response, time to clinical response, safety profile, disease-free survival (DFS), breast-conserving surgery rate and biomarker assessment.

The TRYPHAENA study (ToleRabilitY of Pertuzumab, Herceptin and AnthracyclinEs in NeoAdjuvant breast cancer) is a randomized, multi-centre phase II study that was conducted in 225 people with HER2-positive locally advanced, inflammatory or early-stage breast cancer. 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, progression-free survival (PFS), overall survival (OS) and biomarker assessment.

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.

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