Investor Update

Basel, 25 September 2014

Roche's Avastin and Xeloda show benefit for women with HER2-negative metastatic breast cancer in two new Phase III studies

  • Phase III IMELDA study demonstrates a near threefold increase in progression-free survival and an improvement in overall survival of over 15 months with Avastin plus Xeloda
  • Phase III TANIA study shows a significant improvement in progression-free survival when Avastin-based therapy is continued in the second-line setting following initial treatment with Avastin-based therapy

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the phase III IMELDA study which showed that the combination of Avastin (bevacizumab) plus Xeloda (capecitabine) chemotherapy as a maintenance treatment following initial induction treatment with Avastin-based therapy resulted in clinically meaningful gains in overall survival (OS) and progression-free survival (PFS) in women with HER2-negative metastatic breast cancer. The study met its primary endpoint, with a near threefold improvement in the time that patients lived without their disease getting worse (PFS) when treated with Avastin plus Xeloda maintenance treatment compared to Avastin alone (median PFS after induction treatment: 11.9 months vs. 4.3 months; HR=0.38, p<0.001). It also demonstrated that women lived for an average of 15.3 months longer (OS) when treated with combination maintenance (median OS: 39.0 months vs. 23.7 months, HR=0.43, p<0.001), which was a secondary endpoint of the study. The safety findings of the study were consistent with the known safety profiles of Avastin or Xeloda.

A second positive phase III study (TANIA) showed that women who received Avastin plus standard chemotherapy as initial treatment for their HER2-negative metastatic breast cancer and then continued with Avastin plus chemotherapy after their disease had progressed (in the second-line setting), lived significantly longer without their disease getting worse, compared with people who received chemotherapy alone second-line. The TANIA study met its primary endpoint of improving PFS, with a statistically significant 25 percent reduction in the risk of tumour progression for women who received Avastin plus chemotherapy in the second-line compared to chemotherapy alone (median PFS: 6.3 months vs 4.2 months; HR=0.75, p=0.0068). Safety findings were consistent with the known profiles of Avastin and Xeloda (the most frequently chosen chemotherapy in the second-line setting).

Full results of the IMELDA study will be presented on Sunday 28 September, 2:10 to 3:45 pm CEST, in the Madrid room at the European Society of Medical Oncology (ESMO) 2014 Congress by Joseph Gligorov, M.D; PhD, Principal Investigator of the IMELDA study, Head of the Cancer Coordination Center HUEP and Breast Cancer Expert Center at the APHP Tenon-University Cancer Institute - Pierre & Marie Curie, Sorbonne University, Paris, France.

Full results of the TANIA study will be presented on Sunday 28 September, 2:10 to 3.45 pm CEST, in the Madrid room at the ESMO 2014 congress by Gunter von Minckwitz, M.D, PhD, Principal Investigator of the TANIA study, Chairman of the German Breast Group, Neu-Isenburg, and Professor of Gyneacology at the University Women’s Hospital, Frankfurt, Germany.

Both the IMELDA and TANIA studies have been accepted for publication with The Lancet Oncology, with an anticipated publication date of 28th September 2014.

Avastin is currently approved in the European Union (EU) for use in combination with paclitaxel for the first-line (initial) treatment of adult patients with metastatic breast cancer. Avastin is also approved in the EU in combination with Xeloda for the first-line treatment of adult patients with metastatic breast cancer, in whom treatment with other chemotherapy options, including taxanes or anthracyclines, is not considered appropriate. It is recommended that Avastin treatment is continued until progression of the underlying disease or until unacceptable toxicity.

About the IMELDA study

IMELDA is an open label, randomised, multicentre phase III study that investigated the efficacy and safety of maintenance treatment with Avastin plus Xeloda chemotherapy compared to Avastin alone, in patients whose HER2-negative metastatic breast cancer had not progressed during first-line induction treatment with Avastin plus docetaxel chemotherapy. The primary endpoint was progression-free-survival (PFS) from randomisation following the induction phase; secondary endpoints included overall survival (OS) from randomisation following the induction phase, overall response rate (ORR) and safety.

Results from 185 patients treated showed:

  • The study met its primary endpoint of improving progression-free survival (PFS), with a statistically significant 62 percent reduction in the risk of tumour progression for women who received maintenance treatment with Avastin plus Xeloda compared to those who received maintenance with Avastin alone (median PFS after induction treatment: 11.9 months vs 4.3 months; HR=0.38, p<0.001).
  • In addition, the study demonstrated significantly improved overall survival (OS), with a statistically significant 57 percent reduction in risk of death for women who received maintenance treatment with Avastin plus Xeloda compared to women who received maintenance with Avastin alone (median OS after induction: 39.0 months vs. 23.7 months, HR=0.43 p<0.001). OS was a secondary endpoint of the study.
  • Overall safety findings were consistent with those seen in previous trials of Avastin and Xeloda across tumour types for their approved indications, respectively.

About the TANIA study

TANIA is an open-label, randomised, multicentre phase III trial evaluating the efficacy and safety of Avastin-based therapy in the second-line setting in patients treated with Avastin plus chemotherapy as an initial (first-line) treatment for HER2-negative metastatic breast cancer. The primary endpoint was second-line progression-free-survival (PFS), defined as the time from randomisation to second progression or death; secondary endpoints included overall survival (OS) from randomisation, overall response rate (ORR) and safety. Results from 494 patients showed:

  • The study met its primary objective of improving PFS in the second-line, significantly reducing the risk of tumour progression by 25 percent with the addition of Avastin to chemotherapy compared to chemotherapy alone in women with HER2-negative metastatic breast cancer. Median PFS in the second-line was 6.3 months vs 4.2 months, respectively (HR=0.75, p=0.0068).
  • Further data, including OS, are expected in 2015.
  • Overall safety findings were consistent with those seen in previous trials of Avastin across tumour types for approved indications.

TANIA investigates an unapproved use of Avastin in metastatic breast cancer. Avastin is not licensed in the EU for the second-line treatment of patients with metastatic breast cancer.

About breast cancer

Breast cancer is the most common cancer among women worldwide and approximately one in every eight women will be diagnosed with this disease.1,2 Each year about 350,000 new cases of breast cancer are diagnosed in the European Union, and about 90,000 women will die of the disease annually.3 Four out of every five women diagnosed with breast cancer will have HER2-negative breast cancer.4

About Avastin – 10 years of transforming cancer care

With the initial approval in the United States for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer and ovarian cancer, and is available in the United States for the treatment of colorectal cancer, non-small cell lung cancer, kidney cancer and cervical cancer. In addition, Avastin is approved in the United States and over 60 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over 1.4 million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.

About Avastin – mechanism of action

An independent blood supply is critical for a tumour to grow beyond a certain size (2mm) and spread (metastasise) to other parts of the body. Tumours develop their own blood supply in a process called angiogenesis by releasing vascular endothelial growth factor (VEGF) – a key driver for tumour growth. Avastin is an antibody that precisely targets and inhibits VEGF. Precise VEGF inhibition by Avastin allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments with limited additional impact on the side effects of these therapies.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
1. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Last accessed September 2014 at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx
2. National Cancer Institute. Breast Cancer Risk in American Women. Last accessed September 2014 at http://www.cancer.gov/cancertopics/factsheet/detection/probability-breast-cancer
3. EUCAN. Breast cancer. Last accessed September 2014 at http://eu-cancer.iarc.fr/eucan/CancerOne.aspx?Cancer=46&Gender=2
4. Wolff et al. Arch Pathol Lab Med 2007: 131; 18-43