CHICAGO, IL, USA I June 3, 2012 I Genentech, a member of the Roche Group (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 people 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<0.0001). The EMILIA study is the first randomized Phase III trial of trastuzumab emtansine in people with HER2-positive mBC who had previously received Herceptin® (trastuzumab) and a taxane chemotherapy.
There was also a trend for people 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 people 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 57.0 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, June 3, 1:45 p.m. CDT). The EMILIA data were also featured in the official ASCO press program on Saturday, June 2.
“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, Genentech and Roche plan to submit applications for trastuzumab emtansine in HER2-positive mBC this year to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).
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 signaling and deliver the chemotherapy directly inside HER2-positive cancer cells.
EMILIA 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 people receiving trastuzumab emtansine (n=495) lived without their disease getting worse compared to those who received lapatinib plus Xeloda (n=496), as assessed by independent review: median PFS was 9.6 months compared to 6.4 months, respectively.
The first interim OS analysis demonstrated a trend towards improved OS in people receiving trastuzumab emtansine compared to those who received lapatinib plus Xeloda: median OS was 23.3 months for people who received lapatinib plus Xeloda but had not been reached for people 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 people who received trastuzumab emtansine was 84.7 percent compared to 77.0 percent for people who received lapatinib plus Xeloda. Two-year survival was 65.4 percent compared to 47.5 percent, respectively.
The response rate (the percentage of people with tumor shrinkage) was 43.6 percent for those who received trastuzumab emtansine compared to 30.8 percent for people who received lapatinib plus Xeloda.
The time-to-symptom progression, a patient-reported measure of quality of life, was also improved in people who received trastuzumab emtansine: 7.1 months in people who received trastuzumab emtansine compared to 4.6 months in people who received lapatinib plus Xeloda.
Fewer people who received trastuzumab emtansine experienced Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda, at 40.8 percent compared to 57.0 percent, respectively. For people receiving trastuzumab emtansine, compared to those receiving lapatinib plus Xeloda, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (12.9 percent vs. 0.2 percent), increased levels of enzymes released by the liver and other organs (in most people, these levels had returned to normal by the time of the next dose of trastuzumab emtansine; aspartate aminotransferase: 4.3 percent vs. 0.8 percent; alanine aminotransferase: 2.9 percent vs. 1.4 percent) and anemia (2.7 percent vs. 1.6 percent).
For those people receiving lapatinib plus Xeloda compared to those receiving trastuzumab emtansine, the most common Grade 3 or higher AEs were diarrhea (20.7 percent vs. 1.6 percent), hand-foot syndrome (16.4 percent vs. 0 percent) and vomiting (4.5 percent vs. 0.8 percent).
About the EMILIA Study
EMILIA (TDM4370g/BO21977) is an international, Phase III, randomized, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 people 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 independent review) and OS. Safety profile is also a primary endpoint of the study. Other study endpoints include one-year and two-year survival rates, 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 DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signaling and deliver the chemotherapy 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 people 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 25 ADCs in the pipeline.
About Breast Cancer
Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as “HER2 positivity” and effects approximately 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
SOURCE: Genentech
Post Views: 73
CHICAGO, IL, USA I June 3, 2012 I Genentech, a member of the Roche Group (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 people 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<0.0001). The EMILIA study is the first randomized Phase III trial of trastuzumab emtansine in people with HER2-positive mBC who had previously received Herceptin® (trastuzumab) and a taxane chemotherapy.
There was also a trend for people 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 people 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 57.0 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, June 3, 1:45 p.m. CDT). The EMILIA data were also featured in the official ASCO press program on Saturday, June 2.
“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, Genentech and Roche plan to submit applications for trastuzumab emtansine in HER2-positive mBC this year to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).
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 signaling and deliver the chemotherapy directly inside HER2-positive cancer cells.
EMILIA 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 people receiving trastuzumab emtansine (n=495) lived without their disease getting worse compared to those who received lapatinib plus Xeloda (n=496), as assessed by independent review: median PFS was 9.6 months compared to 6.4 months, respectively.
The first interim OS analysis demonstrated a trend towards improved OS in people receiving trastuzumab emtansine compared to those who received lapatinib plus Xeloda: median OS was 23.3 months for people who received lapatinib plus Xeloda but had not been reached for people 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 people who received trastuzumab emtansine was 84.7 percent compared to 77.0 percent for people who received lapatinib plus Xeloda. Two-year survival was 65.4 percent compared to 47.5 percent, respectively.
The response rate (the percentage of people with tumor shrinkage) was 43.6 percent for those who received trastuzumab emtansine compared to 30.8 percent for people who received lapatinib plus Xeloda.
The time-to-symptom progression, a patient-reported measure of quality of life, was also improved in people who received trastuzumab emtansine: 7.1 months in people who received trastuzumab emtansine compared to 4.6 months in people who received lapatinib plus Xeloda.
Fewer people who received trastuzumab emtansine experienced Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda, at 40.8 percent compared to 57.0 percent, respectively. For people receiving trastuzumab emtansine, compared to those receiving lapatinib plus Xeloda, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (12.9 percent vs. 0.2 percent), increased levels of enzymes released by the liver and other organs (in most people, these levels had returned to normal by the time of the next dose of trastuzumab emtansine; aspartate aminotransferase: 4.3 percent vs. 0.8 percent; alanine aminotransferase: 2.9 percent vs. 1.4 percent) and anemia (2.7 percent vs. 1.6 percent).
For those people receiving lapatinib plus Xeloda compared to those receiving trastuzumab emtansine, the most common Grade 3 or higher AEs were diarrhea (20.7 percent vs. 1.6 percent), hand-foot syndrome (16.4 percent vs. 0 percent) and vomiting (4.5 percent vs. 0.8 percent).
About the EMILIA Study
EMILIA (TDM4370g/BO21977) is an international, Phase III, randomized, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 people 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 independent review) and OS. Safety profile is also a primary endpoint of the study. Other study endpoints include one-year and two-year survival rates, 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 DM1 attached together using a stable linker. Trastuzumab emtansine is designed to target and inhibit HER2 signaling and deliver the chemotherapy 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 people 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 25 ADCs in the pipeline.
About Breast Cancer
Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 229,000 people will be diagnosed with breast cancer, and 40,000 will die from the disease in 2012. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as “HER2 positivity” and effects approximately 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
SOURCE: Genentech
Post Views: 73
