Roche, the world’s largest biotech company, has updated survival results from the phase III CLEOPATRA study, which showed that the combination of Perjeta (pertuzumab), Herceptin (trastuzumab) and docetaxel chemotherapy significantly extended the lives (overall survival) of people with previously untreated HER2-positive metastatic breast cancer (mBC), compared to Herceptin, chemotherapy and placebo.

Results showed that the risk of death was reduced by 34 per cent for people who received Perjeta, Herceptin and chemotherapy, compared to those who received Herceptin and chemotherapy (HR=0.66; p=0.0008). At the time of the analysis, median overall survival had not yet been reached in people receiving the Perjeta combination, as more than half of these people continued to survive. Median overall survival was more than 3 years (37.6 months) for people who received Herceptin and chemotherapy. Based on these data, people receiving Herceptin and chemotherapy in CLEOPATRA have been offered the option to receive Perjeta. No new safety signals were observed in the study.

“This treatment combination with Perjeta is the first to have significantly extended survival compared to Herceptin and chemotherapy in people with previously untreated HER2-positive metastatic breast cancer,” said Hal Barron, MD, Roche’s CMO and head, Global Product Development. “These data further demonstrate that Perjeta is an important new medicine for people with this aggressive 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. Perjeta is believed to work in a way that is complementary to Herceptin, as the two medicines target different places on the HER2 receptor.

In June 2012, the US FDA approved Perjeta in combination with Herceptin and docetaxel chemotherapy for the treatment of people with HER2-positive mBC, who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease, based on the results of the CLEOPATRA study. Perjeta was approved by Swissmedic in August 2012 and in Mexico in September 2012 for the treatment of people with HER2-positive mBC who have not received prior therapy for their metastatic disease. Roche has submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for Perjeta for people with previously untreated HER2-positive metastatic breast cancer.

These final, confirmatory survival data from the CLEOPATRA study will be presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. This data was presented by Dr Sandra Swain, Medstar Washington Hospital Centre, USA.

CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, phase III, randomised, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of Perjeta combined with Herceptin and docetaxel chemotherapy compared to Herceptin and docetaxel chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC, or with HER2-positive mBC that had come back after prior therapy in the adjuvant or neo-adjuvant setting.

The primary endpoint of the study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints were overall survival, PFS by investigator assessment, safety profile, overall response rate (ORR), duration of response and time to symptom progression. PFS and safety data from CLEOPATRA were presented at SABCS 2011 and simultaneously published in the New England Journal of Medicine.

People who received the combination of Perjeta, Herceptin and chemotherapy had a statistically significant 38 per cent reduction in the risk of their disease worsening or death (PFS, HR=0.62, p-value=<0.0001) compared to people who received Herceptin, chemotherapy and placebo.

The median PFS improved by 6.1 months from 12.4 months for people who received Herceptin and chemotherapy to 18.5 months for those who received Perjeta, Herceptin and chemotherapy.

The most common adverse events (rate greater than 30 per cent) seen with the combination of Perjeta, Herceptin and chemotherapy were diarrhoea, hair loss, low white blood cell count with or without fever, upset stomach, fatigue, rash and peripheral neuropathy (numbness, tingling or damage to the nerves). The most common Grade 3–4 adverse events (rate greater than two per cent) were low white blood cell count with or without fever, decrease in a certain type of white blood cell, diarrhoea, damage to the nerves, decrease in red blood cell count, weakness and fatigue).

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, Herceptin and docetaxel chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways.