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Roche Cancer Breakthroughs: difficult to treat recurrent Ovarian, metatastic Colorectal and HER2-positive metastatic breast cancer studies
 
 
  "Roche's Genentech unit has 25 such agents under development for different cancers, including eight in human studies"

3 Media Releases

Basel, 3 June 2012

Roche data showed that people with metastatic colorectal cancer lived longer when they continued on Avastin plus chemotherapy

First phase III study to appraise continued Avastin through different lines of therapy

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from ML18147, a phase III study in metastatic colorectal cancer (mCRC) that evaluated Avastin (bevacizumab) continued with second-line chemotherapy in people who received initial Avastin plus first-line chemotherapy.

The study met its primary endpoint of a significant increase in overall survival (OS). In the study, the relative risk of death was reduced by 19 percent for people who continued with Avastin plus second-line chemotherapy compared with those who received chemotherapy alone (HR = 0.81, p = 0.0062). People who continued with Avastin plus second-line chemotherapy also experienced a significant improvement in progression free survival (PFS, the time a person lives without the disease getting worse); the risk of their cancer progressing was reduced by 32 percent (HR = 0.68, p<0.0001). Adverse events in ML18147 were consistent with those seen in previous pivotal trials of Avastin across tumour types.

"Our study design was based on previous research showing that sustained VEGF inhibition achieved and maintained anti-tumour activity," said Hal Barron M.D., chief medical officer and head, Global Product Development. "While conventional practice is to change treatment completely at disease progression, the continued use of Avastin with a new chemotherapy regimen in this study resulted in patients living longer, compared to a new chemotherapy regimen alone."

These results were featured in a press briefing on Saturday, June 2nd at the 48th Annual Meeting of the American Society of Clinical Oncology. Full results will be presented in the ASCO Gastrointestinal (Colorectal) Cancer Oral Abstracts session by Professor Dirk Arnold, the ML18147 Principal Investigator and Associate Professor of Medicine at the Department of Haematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany (Abstract CRA3503, Sunday, June 3, 10:45 a.m. CDT).

ML18147 Study Results

· People with mCRC who received Avastin in combination with standard chemotherapy in both the first- and second-line settings had a median OS of 11.2 months compared to 9.8 months for people who received chemotherapy alone.

· Median PFS was 5.7 months compared to 4.1 months.

· OS and PFS were calculated from the time patients were randomised to the second-line treatment.

About the ML18147 study

ML18147 was a randomised, open-label phase III multicentre, multinational trial evaluating the efficacy and safety profile of Avastin plus standard second-line chemotherapy in 820 patients with mCRC whose disease had progressed following Avastin plus standard first-line chemotherapy (irinotecan or oxaliplatin-based).

Patients were randomised at progression to one of two treatment arms:

· Arm A: Chemotherapy* plus Avastin (equivalent of 2.5 mg/kg i.v. per week)

· Arm B: Chemotherapy* alone

*Depending on the first-line chemotherapy backbone (fluoropyrimidine / irinotecan-based or fluoropyrimidine / oxaliplatin-based) the chemotherapy backbone was switched in the second-line setting.

The primary endpoint of the study was overall survival measured from the time patients were randomised to the second-line treatment. The secondary efficacy endpoints of the study included PFS, overall response rate and safety profile.

About metastatic Colorectal Cancer (mCRC)

Colorectal cancer is one of the most common cancers in the world, with over 1.2 million new cases diagnosed each year; it is the second most common cancer in women and the third most common cancer in men.1

Despite improvements in screening for early diagnosis, colorectal cancer remains one of the biggest cancer killers in the world and is responsible for over 600,000 deaths each year.1,2

In general the current treatment options for colorectal cancer are surgery, chemotherapy, and biological therapies. Early-stage (localised) cancer has the potential to be cured if the tumour can be successfully surgically removed. Patients with advanced (metastatic) disease are usually treated with chemotherapy after surgery, known as 'first-line' treatment. Many people initially respond to chemotherapy, but unfortunately, in the majority of cases the disease eventually progresses after first-line treatment and patients may require a further round of treatment ('second-line'). There is therefore a real need for effective, tolerable treatments for long-term disease control in metastatic colorectal cancer.

About Avastin: Over 7 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 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 US for the treatment of colorectal cancer, non-small cell lung cancer and kidney cancer. In addition, Avastin is approved in the US and over 30 other countries for the treatment of patients with glioblastoma (a type of brain cancer). Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer and breast 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 one 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: Mode 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 for continuous tumour control. Avastin's precise VEGF inhibition 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, 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 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 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.

1 WHO, IARC GLOBOCAN, Cancer Incidence and Mortality Worldwide in 2008 at http://globocan.iarc.fr/

2 Edwards BK et al. Annual Report to the Nation on the Status of Cancer, 1975-2006, Featuring Colorectal Cancer Trends and Impact of Interventions (Risk Factors, Screening, and Treatment) to Reduce Future Rates. Cancer (2009) 116(3):544-573

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Media Release
Basel, 2 June 2012

Roche study showed that adding Avastin to chemotherapy cut the risk of the disease getting worse in difficult-to-treat recurrent ovarian cancer by half

First phase III study of Avastin plus chemotherapy in platinum-resistant ovarian cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from AURELIA, a phase III study that evaluated treatment with Avastin (bevacizumab) in combination with standard chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) in women with ovarian cancer whose disease had worsened due to resistance to platinum-containing chemotherapy. The risk of progression was reduced by 52 percent in women who received Avastin plus chemotherapy compared with those who received chemotherapy alone (HR = 0.48, p<0.001). The study met its primary endpoint of a significant improvement in progression free survival (PFS, the time a woman lives without the disease getting worse). Adverse events in AURELIA were consistent with those seen in previous pivotal trials of Avastin across tumour types.

These results were featured in a press briefing on Friday, June 1 at the 48th Annual Meeting of the American Society of Clinical Oncology. Full results will be presented in the ASCO Gynaecologic Cancer Oral Abstract session by Professor Eric Pujade-Lauraine, the AURELIA Principal Investigator and Head of the Medical Oncology Dept., Hopitaux Universitaires, Paris Centre, Hopital Hotel-Dieu (Abstract LBA5002, Saturday 2 June, 3:30 p.m. CDT).

"Most women with advanced ovarian cancer will experience disease progression after treatment, and almost all of them will at some stage of the disease have cancer that is resistant to platinum-based chemotherapy which severely limits treatment options," said Hal Barron M.D., Chief Medical Officer and Head Global Product Development. "Adding Avastin to chemotherapy for women with advanced ovarian cancer in this study reduced their risk of cancer progression by half."

In December 2011 Avastin received European approval for use in the front-line treatment of advanced ovarian cancer, based on the results from GOG 0218 and ICON7. Roche will share the AURELIA data with health authorities and discuss appropriate next steps.

AURELIA Study Results

· Women with recurrent, platinum-resistant ovarian cancer who received Avastin in combination with chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) had a median progression free survival of 6.7 months compared to 3.4 months in women who received chemotherapy alone.

· In addition, they had a significantly higher rate of tumor shrinkage (objective response rate, ORR) compared to women who received chemotherapy alone (30.9 percent versus 12.6 percent, p=0.001).

AURELIA is the fourth phase III study of Avastin in ovarian cancer (following GOG 0218, ICON7 and OCEANS) to show that adding Avastin to chemotherapy significantly increased the time women with this disease lived without their disease getting worse.

About the AURELIA study

AURELIA is a multicentre, randomised, open-label, two-arm phase III study in 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. Women in AURELIA had received no more than two anticancer regimens prior to enrolment in the trial. The trial was designed to evaluate Avastin (10mg/kg every two weeks or 15mg/kg every three weeks) in combination with standard chemotherapy (either weekly paclitaxel or topotecan or pegylated liposomal doxorubicin) compared to standard chemotherapy alone.

The trial was set up in cooperation with the Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and was conducted by the international network of the Gynecologic Cancer Intergroup (GCIG) and the pan-European Network of Gynaecological Oncological Trial Groups (ENGOT). The primary endpoint of the study was progression-free survival. The secondary endpoints of the study included overall survival, objective response rate, Quality of Life, safety and tolerability.

When treating ovarian cancer, the time between receiving the last dose of platinum-based chemotherapy and disease recurrence is used to help determine the choice of chemotherapy used in the next line of treatment. Patients are said to have 'platinum-resistant' disease if their disease worsens between one and six months of completing their platinum-based chemotherapy, and 'platinum-sensitive' disease if it worsens more than six months after.

About Ovarian Cancer

Ovarian cancer is the eight most commonly diagnosed cancer in women and the seventh 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. Surgery to remove as much of the tumour as possible is a mainstay of treatment but unfortunately, the majority of patients are diagnosed with late stage disease (when the cancer has grown or spread) and they require further treatment.

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 ascites development (excess fluid in the abdominal cavity), disease worsening, and a poorer prognosis in women with ovarian cancer. Avastin is designed to specifically target VEGF.

About Avastin: Over 7 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 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 US for the treatment of colorectal cancer, non-small cell lung cancer and kidney cancer. In addition, Avastin is approved in the US and over 30 other countries for the treatment of patients with glioblastoma (a type of brain cancer). Avastin is approved in Japan for the treatment of the advanced stages of colorectal, non-small cell lung cancer and breast 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 one 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: Mode 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 for continuous tumour control. Avastin's precise VEGF inhibition 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, 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 personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 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) WHO, IARC GLOBOCAN, Cancer Incidence and Mortality Worldwide in 2008

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Media Release
Basel, 3 June 2012

Roche's targeted investigational breast cancer medicine, trastuzumab emtansine (T-DM1), reduced the risk of cancer worsening or death by 35 percent in pivotal phase III trial

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the Phase III EMILIA study of trastuzumab emtansine (T-DM1) met its co-primary endpoint, of a significant improvement in the time patients with HER2-positive metastatic breast cancer (mBC) lived without their disease getting worse (progression-free survival; PFS). The study showed that the risk of disease worsening or death was reduced by 35 percent for people who received trastuzumab emtansine compared to those who received lapatinib plus Xeloda® (capecitabine) chemotherapy (HR=0.65, p-value <.0001). The EMILIA study is the first randomised Phase III trial of trastuzumab emtansine in patients with HER2-positive mBC who had previously received Herceptin® (trastuzumab) and a taxane chemotherapy.

There was also a trend for patients who received trastuzumab emtansine to live longer (overall survival, or OS, the other co-primary endpoint of the study) than those who received lapatinib plus Xeloda, but these data are currently not mature. The safety profile of trastuzumab emtansine was consistent with that seen in previous studies, with fewer patients who received trastuzumab emtansine experiencing Grade 3 or higher (severe) adverse events (AEs) than those who received lapatinib plus Xeloda (40.8 percent compared to 57 percent).

The EMILIA data will be presented in the plenary session at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago by Kim Blackwell, M.D., Duke University School of Medicine (Abstract #LBA1, Sunday 3 June at 1:45 pm CDT). The EMILIA data were also featured in the official ASCO press programme on Saturday 2 June.

"The encouraging efficacy, safety profile and quality of life results from the EMILIA study support our belief that trastuzumab emtansine may have an important role for patients with HER2-positive metastatic breast cancer," said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. "We are working with global regulatory authorities to submit these data as quickly as possible and hope that trastuzumab emtansine will soon be available to patients with this aggressive type of breast cancer."

Based on the EMILIA findings, Roche and Genentech plan to submit applications for trastuzumab emtansine in HER2-positive mBC this year to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).

Trastuzumab emtansine is an investigational medicine known as an antibody-drug conjugate (ADC). It is comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signalling and deliver the chemotherapy directly inside HER2-positive cancer cells.

Study results

· The results presented at ASCO represent the final analysis of PFS and the first interim analysis of OS.

· There was a significant improvement in the time patients receiving trastuzumab emtansine (n=495) lived without their disease getting worse compared to those who received lapatinib plus Xeloda (n=496), as assessed by an independent review committee: median PFS was 9.6 months versus 6.4 months, respectively.

· The first interim OS analysis demonstrated a trend towards improved OS in patients receiving trastuzumab emtansine versus those who received lapatinib plus Xeloda: median OS was 23.3 months for patients who received lapatinib plus Xeloda but had not been reached for patients receiving trastuzumab emtansine and requires longer follow-up (HR=0.62; P=0.0005).

· As the hazard ratio for OS did not cross the pre-specified stopping boundary for the study, the OS analysis is not considered statistically significant at this time. The final analysis is expected to take place by 2014.

· One-year survival in patients who received trastuzumab emtansine was 84.7 percent versus 77.0 percent for patients who received lapatinib plus Xeloda. Two-year survival was 65.4 percent versus 47.5 percent, respectively.

· The response rate (the percentage of patients with tumour shrinkage) was 43.6 percent for those who received trastuzumab emtansine versus 30.8 percent of patients who received lapatinib plus Xeloda.

· The time-to-symptom progression, a patient-reported measure of quality of life, was also improved in patients who received trastuzumab emtansine: 7.1 months in patients who received trastuzumab emtansine versus 4.6 months in patients who received lapatinib plus Xeloda.

· Fewer patients who received trastuzumab emtansine experienced Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda, at 40.8 percent versus 57 percent, respectively. For people receiving trastuzumab emtansine, compared to those receiving lapatinib plus Xeloda, the most common (occurring in more than 2 percent of patients) Grade 3 or higher AEs were low platelet count (12.9 percent versus 0.2 percent), increased levels of enzymes released by the liver and other organs (in most patients these levels had returned to normal by the time of the next dose of trastuzumab emtansine; aspartate aminotransferase: 4.3 percent versus 0.8 percent; alanine aminotransferase: 2.9 percent versus 1.4 percent) and anaemia (2.7 percent versus 1.6 percent).

· For those patients receiving lapatinib plus Xeloda compared to those receiving trastuzumab emtansine, the most common Grade 3 or higher AEs were diarrhoea (20.7 percent versus 1.6 percent), hand-foot syndrome (16.4 percent versus 0) and vomiting (4.5 percent versus 0.8 percent).

About the EMILIA study

EMILIA (TDM4370g/BO21977) is an international, Phase III, randomised, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 patients with HER2-positive locally advanced or metastatic breast cancer whose disease progressed after initial treatment with Herceptin and a taxane-based chemotherapy.

Participants in the trastuzumab emtansine arm received:

· Trastuzumab emtansine 3.6 mg/kg dose every three weeks

Participants in the lapatinib plus Xeloda arm received:

· Lapatinib 1250 mg dose daily, every three weeks.

· Xeloda 1000 mg/m2 dose, twice daily, days 1 - 14, every three weeks.

The co-primary efficacy endpoints of the study are PFS (as assessed by an independent review committee) and OS. Safety is also a primary endpoint of the study. Other study endpoints include and one-year and two-year survival rates, safety profile, PFS as assessed by investigator, objective response rate, duration of response and quality of life.

About trastuzumab emtansine

Trastuzumab emtansine is an ADC being studied in HER2-positive cancers. It is comprised of the antibody trastuzumab and the chemotherapy agent DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signalling and deliver the chemotherapy agent DM1 directly inside HER2-positive cancer cells. Trastuzumab emtansine binds to the HER2-positive cancer cells, and is thought to block out-of-control signals that make the cancer grow while also calling on the body's immune system to attack the cancer cells. Once trastuzumab emtansine is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1.

In addition to EMILIA, there are two ongoing Phase III studies of trastuzumab emtansine:

· MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in patients with HER2-positive mBC who have not been previously treated for their metastatic disease.

· TH3RESA is comparing trastuzumab emtansine to physician's choice of treatment in people with HER2-positive mBC who have already received both Herceptin and lapatinib.

Genentech, a member of the Roche Group, licenses technology for trastuzumab emtansine under an agreement with ImmunoGen, Inc.

Building on the results of trastuzumab emtansine studies to date, Roche/Genentech have approximately 25ADCs in the pipeline.

About breast cancer

Breast cancer is the most common cancer among women worldwide. 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.1 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.2 HER2-positive cancer is a particularly aggressive form of breast cancer.3

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 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 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. 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.

2. 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.

3. Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.

 
 
 
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