Avastin phase III study shows positive results in women with advanced ovarian cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that a phase III study showed the combination of Avastin (bevacizumab) and chemotherapy followed by maintenance use of Avastin increased the time women with advanced ovarian cancer lived without their disease worsening (progression-free survival or PFS) compared to chemotherapy alone. A preliminary assessment of safety noted adverse events previously observed in pivotal trials with Avastin. Data from the study will be submitted for presentation at the 2010 American Society of Clinical Oncology (ASCO) annual meeting, June 4 to 8, 2010.

This is the first positive phase III study of an anti-angiogenic therapy in advanced ovarian cancer and continues to support Avastin and anti-angiogenesis as a fundamental pillar of cancer treatment today. Advanced ovarian cancer is a disease where outlook for patients remains poor and new effective therapies are needed. Avastin has shown the potential to provide this new therapy option for physicians and to bring hope to patients and their families.

In the three-arm study, known as Gynecologic Oncology Group (GOG) 0218, women with newly diagnosed advanced ovarian cancer who already had surgery to remove as much of the tumour as possible were randomised to receive one of the following:

* Arm 1: Placebo in combination with commonly-used chemotherapy followed by placebo for a total treatment duration of up to 15 months
* Arm 2: Avastin in combination with commonly-used chemotherapy followed by placebo for a total treatment duration of up to 15 months
* Arm 3: Avastin in combination with commonly-used chemotherapy followed by the continuation of Avastin alone, as maintenance therapy, for a total treatment duration of up to 15 months

The study showed that women who continued maintenance use of Avastin alone, after receiving Avastin in combination with chemotherapy (Arm 3), lived longer without the disease worsening compared to those who received chemotherapy alone. Women who received Avastin in combination with chemotherapy, but did not continue maintenance use of Avastin alone (Arm 2), did not live longer without the disease worsening compared to chemotherapy alone.

“We are greatly encouraged by these results which suggest that Avastin could offer women with advanced ovarian cancer more time without their disease worsening,” said Pascal Soriot, COO of Roche’s Pharmaceutical Division. “Women with this disease still have a poor outlook and we are committed to working with the relevant health authorities to make Avastin available to these patients.”
About ovarian cancer

Ovarian cancer is the sixth most commonly diagnosed cancer in women and the eighth leading cause of cancer death among women worldwide. Annually, an estimated 230,000 women will be diagnosed with ovarian cancer around the world and approximately 140,000 will die from the disease1. Currently, treatment options for women with this disease are limited to surgery, and chemotherapy. Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Studies have shown a correlation between a high concentration of VEGF and a poorer prognosis in women with ovarian cancer. Avastin is designed to specifically target VEGF.
About the GOG 0218 Study

GOG 0218 is a multicenter, randomised, double-blinded, placebo-controlled phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma. The trial evaluates Avastin plus carboplatin and paclitaxel chemotherapy compared to carboplatin and paclitaxel chemotherapy alone. The trial is also designed to assess the continued use of Avastin alone in the maintenance setting following the initial combined regimen of Avastin and chemotherapy.

Patients were randomized to one of three treatment arms each of a duration of up to 15 months (22 cycles):

* ARM 1: Placebo in combination with carboplatin (AUC 6 IV) and paclitaxel (175mg/m2) chemotherapies (6 cycles) followed by placebo alone (22 cycles ,up to 15 months)
* ARM 2: Avastin (15mg/kg; 5 cycles starting at cycle 2) in combination with carboplatin and paclitaxel chemotherapies (6 cycles) followed by placebo alone (22 cycles, up to 15 months)
* ARM 3: Avastin (15mg/kg; 5 cycles starting at cycle 2) in combination with carboplatin and paclitaxel chemotherapies (6 cycles) followed by the maintenance use of Avastin alone (22 cycles, up to 15 months)

The trial is sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between the NCI and Genentech, and is being conducted by a network of researchers led by the Gynecologic Oncology Group (GOG). The primary endpoint of the study is PFS as assessed by trial investigators. Secondary endpoints of the study include overall survival, PFS by independent review, objective response rate, safety, quality of life measures and analysis of patient tumour and blood samples.

Detailed safety assessments are ongoing. Preliminary assessment of safety as performed by the GOG identified bevacizumab related serious AEs noted in previous pivotal studies, including fatal neutropenic infection and gastro-intestinal perforation. The full study results, including safety assessments, will be presented at a future meeting.
About Avastin: Over 5 Years of Transforming Cancer Care

With the initial approval in the USA 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 the US and Europe for the treatment of advanced stages of colorectal cancer, breast cancer, non-small cell lung cancer and kidney cancer, and Avastin is also available in the US for the treatment of patients with advanced brain cancer (glioblastoma). Avastin is the only anti-angiogenic therapy available for the treatment of these numerous advanced cancer types, which collectively cause over 2.5 million deaths each year.1,2,3

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today – over half a million patients have been treated with Avastin so far. A comprehensive clinical programme with over 450 clinical trials is investigating the use of Avastin in various tumour types (including colorectal, breast, non-small cell lung, brain, gastric, ovarian, prostate and others) and different settings (advanced or early stage disease).
About Avastin: Mode of Action

Avastin is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis – a fundamental process required for a tumour to grow and to spread (metastasise) to other parts of the body. Avastin’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Avastin helps to control tumour growth and extend survival with only a limited impact on the side effects of chemotherapy.
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, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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References
1.Garcia M et al. Global Cancer Facts & Figures. Atlanta, GA: American Cancer Society, 2007
2.WHO Cancer Factsheet N°297 – updated July 2008. Last accessed 24 March 2009 at http://www.who.int/mediacentre/factsheets/fs297/en/index.html.
3.Parkin DM et al. CA Cancer J Clin 2005; 55: 74-108.