Roche obtains EU approval for PERJETA

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency (EMA) has approved PERJETA(pertuzumab) for patients with previously untreated HER2-positive metastatic breast cancer (mBC). PERJETA is approved in combination with Herceptin (trastuzumab) and docetaxel in adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer, who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease.

“The EU approval of Perjeta is the result of years of research into the HER2 pathway and we are excited to offer a new treatment option for people with this aggressive disease,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. “The combination of Perjeta, Herceptin and chemotherapy is the first to significantly extend survival compared to the previous standard of care, Herceptin and chemotherapy alone.”

The European approval comes after the Phase III CLEOPATRA trial showed that the combination of PERJETA, Herceptin and chemotherapy provided patients with a median of 6.1 months longer without their disease worsening or death (progression-free survival, PFS) and provided a 34 percent reduction in the risk of death (overall survival) compared to Herceptin and chemotherapy alone.

PERJETA is an example of Roche’s Personalised Healthcare Approach as it targets the HER2 receptor, a protein found in high quantities on the outside of HER2-positive breast cancer cells. A diagnostic HER2 test is used to determine if a patient has HER2-positive breast cancer. PERJETA is believed to work in a way that is complementary to Herceptin, as the two medicines target different regions on the HER2 receptor. Herceptin was the first monoclonal antibody developed for the treatment of HER2-positive breast cancer and has increased survival times for patients so that they are now the same as for patients with HER2-negative breast cancer. Before Herceptin treatment, shorter survival outcomes were expected for patients diagnosed with HER2-positive breast cancer, compared to patients with HER2-negative disease.1 In the CLEOPATRA study, PERJETA in combination with Herceptin and chemotherapy has shown the extension of survival times for patients with this aggressive disease even further than Herceptin.

PERJETA is now approved in the EU, the US, and Switzerland for the treatment of people with HER2-positive mBC who have not received prior therapy for their metastatic disease. Further country approvals are anticipated during 2013.

About PERJETA

PERJETA is designed specifically to prevent the HER2 receptor from pairing (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 combination of PERJETA, Herceptin and chemotherapy is thought to provide a more comprehensive blockade of HER signalling pathways.

About the CLEOPATRA study

CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, phase III, randomised, double-blind, placebo-controlled study.2 The study evaluated the efficacy and safety profile of PERJETA combined with Herceptin and docetaxel chemotherapy compared to Herceptin and chemotherapy plus placebo in 808 people with previously untreated HER2-positive mBC or that had returned after prior therapy in the adjuvant (after surgery) or neoadjuvant (before surgery) setting.

The study met its primary endpoint of PFS and its secondary endpoint of OS. People who received the combination of PERJETA, Herceptin and chemotherapy had a statistically significant 38 percent reduction in the risk of their disease worsening or death (progression free survival, PFS; HR=0.62, p-value=<0.0001) compared to people who received Herceptin and chemotherapy.3 The study demonstrated that 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.3 The risk of death was significantly reduced by 34 percent for people who received the combination of PERJETA, Herceptin and chemotherapy compared to those who received Herceptin and chemotherapy (overall survival, HR=0.66; p=0.0008).2 Median overall survival was 37.6 months (more than 3 years) for people who received Herceptin and chemotherapy.2 At the time of the analysis, median overall survival had not yet been reached for people receiving the combination of PERJETA, Herceptin and chemotherapy, as more than half of these people continued to survive.

In CLEOPATRA, the most common adverse reactions (rate greater than 30 percent) 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 2 percent) 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).3

About breast cancer

Breast cancer is the most common cancer among women worldwide.4 Each year, about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually.4 In HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumour cells. This is known as “HER2 positivity” and affects approximately 15-20 percent of women with breast cancer.5 HER2-positive cancer is a particularly aggressive form of breast cancer.6

References

1. Dawood S, et al. Prognosis of Women With Metastatic Breast Cancer by HER2 Status and Trastuzumab Treatment: An Institutional-Based Review. J Clin Oncol. 2010: 28, 92-98
2. Swain S, et al. Confirmatory overall survival analysis of CLEOPATRA: A randomized, double-blind, placebo-controlled Phase III study with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. Poster presentation at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. Abstract # P5-18-26
3. Baselga J, Cortes J, Sung-Bae K, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med.2012; 366:109–119.
4. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr.
5. Wolff A.C et al. American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med—Vol 131, January 2007.
6. Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.