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Roche reports positive data for Avastin in ovarian cancer and T-DM1 in breast cancer


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Encouraging new data released at ESMO congress

* Ovarian cancer: Data from second positive phase III study of Avastin (ICON7) add further evidence to the potential of Avastin in ovarian cancer where there have been few major treatment advances in the past decade1.
* Metastatic breast cancer: T-DM1 achieves efficacy comparable to standard of care while significantly reducing the burden of typical side effects associated with conventional chemotherapy2.

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that new data released at the 35th Congress of the European Society of Medical Oncology (ESMO) congress continue to support Roche’s development programs for Avastin in ovarian cancer and T-DM1 in HER2-positive breast cancer.

“We are committed to developing new medicines that make a difference in the lives of people living with cancer,” said Hal Barron, M.D., Head of Global Development and Chief Medical Officer at Roche. “The clinical data presented today at ESMO further demonstrate that Avastin in ovarian cancer and T-DM1 in HER2-positive breast cancer may improve the treatment of women with ovarian or breast cancer. ”
Ovarian cancer - Avastin

Data from ICON7, the second positive phase III study of Avastin in ovarian cancer, were presented for the first time today at ESMO, adding further evidence to support the potential of Avastin to improve outcomes in a disease for which there have been few treatment advances in over a decade. In ICON7, chemotherapy-naïve ovarian cancer patients who received Avastin in combination with standard chemotherapy and then continued Avastin alone had about 27% improvement in the likelihood of living longer without the disease worsening (progression-free survival or PFS) compared to those women who received only chemotherapy, (hazard ratio = 0.79, corresponding to a 21% reduction in risk of cancer progression or death).

The first phase III pivotal study of Avastin in ovarian cancer, GOG0218, was presented at ASCO earlier this year and showed that Avastin, when combined with standard chemotherapy and then continued alone, improved the likelihood of women living longer without the disease worsening by up to 54% compared to those women who received only chemotherapy (hazard ratio = 0.65).

GOG0218 was conducted with a higher dose of Avastin and longer treatment duration than ICON7. The 3-arm design of the GOG218 trial allowed conclusion that continued use of Avastin for a longer treatment duration improved outcome in this setting. Overall survival data for both studies are currently immature and favour numerically the Avastin-containing study arms.

Ovarian cancer is the sixth most commonly diagnosed cancer in women and the eighth leading cause of cancer death among women worldwide. Surgery to remove as much of the tumour as possible is a mainstay of treatment but is not adequate for the majority of cases, which are diagnosed late when the cancer has grown extensively or spread, and further chemotherapy is often recommended. Recurrence of disease after treatment with current standard chemotherapies is unfortunately common.
Breast cancer - T-DM1

Early positive results from T-DM1 demonstrated efficacy comparable to the current standard of care while exhibiting a better safety profile. The results were shown in the first randomized phase II study comparing trastuzumab-DM1 (T-DM1) to Herceptin (trastuzumab) plus chemotherapy (docetaxel), the current standard of care for first line HER2-positive metastatic breast cancer. Safety data and a preliminary analysis of the objective response rate, a secondary efficacy endpoint, were presented at ESMO’s Presidential Symposium today.

Tumour shrinkage (or objective response rate), was similar in women treated with T-DM1 compared to those treated with Herceptin plus chemotherapy (47.8% vs. 41.4%, p=0.456) with a minimum of 5.9 months of follow-up. Longer follow-up will be required for the analysis of PFS and final, mature objective response rate. Grade 3 or higher adverse events were reported in approximately twice as many patients receiving Herceptin plus chemotherapy (control arm) as in those receiving T-DM1 (75% vs. 37%). The majority of these Grade 3 or higher adverse events were chemotherapy-related and accounted for the difference between the 2 arms of the study.

Most adverse events (all grades) on the Herceptin plus docetaxel arm were alopecia (complete hair loss - 66.2% compared to 1.5% for the T-DM1 arm), neutropenia (reduction in white blood cells – 57.4% vs. 7.5%) and diarrhoea (45.6% vs. 10.4%); most adverse events on the T-DM1 arm were nausea (47.8% vs. 39.7%), fatigue (46.3% vs. 46.2%) and temperature increase (35.8% vs. 20.6%).

This early analysis supports further investigation of this novel antibody-drug conjugate free of conventional chemotherapy in the first line HER2-positive metastatic breast cancer setting. This is currently being tested in the Phase III MARIANNE study3.

It is anticipated that progression-free survival results (the primary end-point) for the TDM4450g study will be available in Q2 2011.
About the phase III studies of Avastin as a front-line treatment of ovarian cancer

* The potential role of Avastin in the front-line (first-line following surgery) treatment of ovarian cancer is supported by results of two large phase III studies (GOG0218 and ICON7), involving over 2,300 patients.
* These studies show that women treated with Avastin in combination with standard chemotherapy (carboplatin and paclitaxel) followed by the continued use of Avastin alone, had a significant improvement in time lived without their disease getting worse (progression-free survival, PFS) compared to women treated with chemotherapy alone.
* Adverse events were consistent with those observed in pivotal trials of Avastin.

About the ICON7 study

* International, multicenter, randomised, open-label, phase III study in 1,528 women with previously untreated epithelial ovarian, primary peritoneal or fallopian tube carcinoma.
* Women who received front-line Avastin (7.5mg/kg) in combination with standard of care chemotherapy (paclitaxel and carboplatin), and continued use of Avastin alone for a total duration of up to 12 months, had a median PFS of 18.3 months compared to 16 months in women who received chemotherapy alone (hazard ratio = 0.79). This is a 21 percent reduction in the risk of cancer progression or death, which corresponds to a 27 percent improvement in the likelihood of living longer without the disease worsening.

ICON-7 data presentation at the 35th European Society for Medical Oncology (ESMO) congress: ESMO Presidential Symposium, Gold Hall, Monday 11 October 16:30 CET: A phase III randomised Gynaecologic Cancer InterGroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), T. Perren et al. (followed by an Invited Discussant at 16:45)
About the GOG0218 study

* International, multicenter, randomized, double-blind, placebo-controlled Phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal or fallopian tube carcinoma who already had surgery to remove as much of the tumour as possible.
* Women who received Avastin (15mg/kg) in combination with chemotherapy (paclitaxel and carboplatin), and continued use of Avastin alone for a total duration of up to 15 months, had a median PFS of 14.1 months compared to 10.3 months in women who received chemotherapy alone (hazard ratio = 0.72). This is a 28 percent reduction in the risk of cancer progression or death, which corresponds to a 39 percent improvement in the likelihood of living longer without the disease worsening.
* The GOG0218 study protocol allowed for different ways to determine if a patient’s disease had progressed (worsened). Disease progression could be measured based exclusively on levels of a protein (CA-125) in the blood, or through the use of CA-125 levels and evidence of progression by a radiograph/scan. (CA-125 is measured by a blood test and is sometimes used to demonstrate a response to chemotherapy or to diagnose a recurrence or progression of ovarian cancer).
* An additional analysis of efficacy was conducted for regulatory purposes that only included disease progressions determined by radiographs/scans (excluding progressions based on CA-125 alone). In this analysis, women who continued Avastin, following Avastin in combination with chemotherapy, had a median PFS of 18.0 months compared to 12.0 months in women who received chemotherapy alone, increasing the likelihood of them living longer without the disease worsening by 54 percent (based on a hazard ratio = 0.65,, which corresponds to a 35 percent reduction in the risk of cancer progression or death).

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 and 27 other countries for the treatment of patients with glioblastoma (a type of brain cancer). 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.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today – over three quarters of a 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 (including colorectal, breast, non-small cell lung, brain, gastric, ovarian 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 the T-DM1 TDM4450g study

The Phase II study (known as TDM4450g) is a randomized, multicentre international, two-arm, open-label clinical trial including 137 patients with first-line HER2-positive metastatic breast cancer. Patients from approximately 64 sites were randomized to receive either T-DM1 or Herceptin and chemotherapy (docetaxel). The primary endpoints of the study are progression-free survival (PFS) and safety. Secondary endpoints include duration of overall survival, objective response, duration of objective response, clinical benefit rate, Pharmacokinetic properties and time to symptom progression. PFS results for the study are not yet mature and are expected in Q2 2011.

Grade 3 or higher adverse events were reported in approximately twice as many patients receiving Herceptin plus chemotherapy (control arm) as in those receiving T-DM1 (75% vs. 37%)3. The majority of these Grade 3 or higher adverse events on the Herceptin plus docetaxel arm were chemotherapy-related.

TDM4450 data presentation at the 35th European Society for Medical Oncology (ESMO) congress: ESMO Presidential Symposium, Gold Hall, Monday 11 October 16:00 CET: Efficacy and safety of trastuzumab-DM1 versus trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients with no prior chemotherapy for metastatic disease: preliminary results of a randomized, multicenter, open-label phase 2 study (followed by an Invited Discussant at 16:15)

About T-DM1

T-DM1 is an antibody-drug conjugate (ADC), also known as an armed antibody, being studied for advanced HER2 positive breast cancer. T-DM1 is designed to combine the clinical benefits of trastuzumab with a potent microtubule-disrupting drug, DM1 (a derivative of maytansine). DM1 is conjugated to trastuzumab through a stable thioether linker designed to keep T-DM1 intact until it reaches specific cancer cells. The antibody (trastuzumab) binds to the HER2 positive cancer cells, and is thought to block out-of-control signals that contribute to cancer growth and survival while also calling on the body’s immune system to attack the cells. Once T-DM1 is internalized into those cancer cells, DM1 containing metabolites of the conjugate specifically destroy the cells. Genentech licenses technology for T-DM1 under an agreement with ImmunoGen, Inc.

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.

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

References
1) T. Perren et al. Avastin ICON7, ESMO 2010, Abstract LBA4
2) E. Perez et al. T-DM1 TDM4450, ESMO 2010, Abstract LBA3
3) The ongoing phase III study, MARIANNE, will compare both T-DM1 alone and T-DM1 in combination with pertuzumab to Herceptin in combination with a taxane chemotherapy in people with advanced HER2 positive breast cancer who have not been previously treated for advanced disease



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