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Applications Submitted in Anemias and of a Biosimilar, European Approval in Breast Cancer, and More

Gina Columbus
Published: Tuesday, Apr 16, 2019



Today-

Applications submitted in anemias and of a biosimilar, a European approval in breast cancer, and breast cancer screening guidance statements issued by the American College of Physicians.

Welcome to OncLive News Network! I’m Gina Columbus.

A supplemental biologics license application has been submitted to the FDA for luspatercept for the treatment of adult patients with very low- to intermediate-risk myelodysplastic syndrome—associated anemia with ring sideroblasts who require red blood cell transfusions, and also for adult patients with beta-thalassemia–associated anemia who require such transfusions.

The application is based on findings from the phase III MEDALIST and BELIEVE studies, which showed that treatment with luspatercept led to RBC transfusion independence in patients with MDS-associated anemia as well as significant reductions in RBC transfusion burden in those with beta-thalassemia–associated anemia.

In MEDALIST, results showed that 37.9% of patients treated with luspatercept experienced RBC transfusion independence for 8 or more weeks compared with 13.2% in the placebo arm. In the BELIEVE trial, 21.4% of patients in the luspatercept arm achieved a 33% or higher reduction in transfusion burden, with a reduction of 2 or more RBC units, during weeks 13 to 24, when compared with a 12-week baseline period versus 4.5% of those on placebo. Specifically, 19.6% patients on luspatercept achieved a 33% or higher reduction in RBC transfusion burden at weeks 37 to 48 compared with 3.6% of those receiving placebo.

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A biologics license application has been resubmitted to the FDA for the pegfilgrastim biosimilar LA-EP2006 to decrease the incidence of infection from febrile neutropenia in patients with nonmyeloid malignancies who are receiving myelosuppressive anticancer therapy. The resubmission addresses a complete response letter the FDA issued in June 2016.

With the resubmission, the application includes new data from a pivotal single-dose, three-period, cross-over, pharmacokinetics and pharmacodynamics study comparing Sandoz’s pegfilgrastim biosimilar with US-sourced reference pegfilgrastim; the pegfilgrastim biosimilar with European Union–sourced reference pegfilgrastim; and US- with EU-sourced reference pegfilgrastim.

At the time of the 2016 CRL, Sandoz had stated that it was working with the FDA to address remaining questions.

Investigators from the phase I trial noted that due to historically known high intra- and inter-subject variabilities with reference biologic in area under the serum concentration-time curve, the study is appropriate and establishes the scientific bridge to demonstrate similarity of PK/PD, safety, and immunogenicity between LA-EP2006, EU reference pegfilgrastim, and US reference pegfilgrastim. As of October 2018, the trial was ongoing in 1 Dutch and 5 US study sites.

The European Commission approved LA-EP2006, known by the trade name Ziextenzo, as a treatment to reduce the duration of neutropenia and incidence of febrile neutropenia that is associated with anticancer chemotherapy in November 2018.

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In breast cancer, the European Commission has approved olaparib for the treatment of adult patients with germline BRCA1/2-mutant, HER2-negative locally advanced or metastatic disease.

The decision is based on findings from the phase III OlympiAD trial, in which the PARP inhibitor reduced the risk of disease progression or death by 42% compared with chemotherapy in patients with germline BRCA-mutant, metastatic disease.

With the indication, patients must have been previously treated with an anthracycline and a taxane in the neoadjuvant or metastatic setting unless they were ineligible to receive them. Additionally, those with hormone receptor—positive breast cancer must have progressed on or following endocrine therapy or be ineligible for the treatment.

In OlympiAD, results showed that the median progression-free survival was 7.0 months with olaparib versus 4.2 months with chemotherapy, demonstrating a statistically significant improvement.

Additionally, the overall response rates were 52% and 23% for olaparib and chemotherapy, respectively. The median duration of response was 6.4 months in the olaparib group and 7.1 months in the standard-therapy arm, and the median time to onset of response was 47 days and 45 days, respectively.

The FDA approved olaparib for this indication in January 2018.

*********************************

New evidence-based guidance statements issued by the American College of Physicians announced that women at average risk for breast cancer who are between the ages of 40 and 49 years, clinicians should have a personalized approach on whether their patients should be screened with mammography prior to the age of 50.

Additionally, the guidance statement reads that those who are at average risk for breast cancer and are between the ages of 50 and 74 with no symptoms of disease should be screened with mammography bi-annually.

These guidance statements do not apply to patients who have had prior abnormal screening results or in higher-risk patients. This includes patients with a personal history of breast cancer, or those who may harbor genetic mutations that are associated with increased risk, such as BRCA1/2 or another familial breast cancer syndrome.

Two additional guidance statements by the ACP state that for women who are at average risk for breast cancer and are 75 years or older, or in women who have a life expectancy of less than10 years, breast cancer screening should be discontinued. Moreover, in average-risk women of all ages, a clinical breast examination should not be used as a method to screen for breast cancer.

Approximately 20% of women diagnosed with breast cancer throughout a 10-year period will be overdiagnosed and likely overtreated. Harms associated with breast cancer screening include overdiagnosis; false-positive results; overtreatment; radiation exposure, as well as radiation associated breast cancers and breast cancer deaths; and anxiety and distress from the corresponding tests and procedures, which include breast biopsies.

*********************************

This week, we sat down with Drs John Marshall, of Georgetown-Lombardi Comprehensive Cancer Center, and Drs Tanios S. Bekaii-Saab, of Mayo Clinic, to discuss dosing strategies and patient support in metastatic colorectal cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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Today-

Applications submitted in anemias and of a biosimilar, a European approval in breast cancer, and breast cancer screening guidance statements issued by the American College of Physicians.

Welcome to OncLive News Network! I’m Gina Columbus.

A supplemental biologics license application has been submitted to the FDA for luspatercept for the treatment of adult patients with very low- to intermediate-risk myelodysplastic syndrome—associated anemia with ring sideroblasts who require red blood cell transfusions, and also for adult patients with beta-thalassemia–associated anemia who require such transfusions.

The application is based on findings from the phase III MEDALIST and BELIEVE studies, which showed that treatment with luspatercept led to RBC transfusion independence in patients with MDS-associated anemia as well as significant reductions in RBC transfusion burden in those with beta-thalassemia–associated anemia.

In MEDALIST, results showed that 37.9% of patients treated with luspatercept experienced RBC transfusion independence for 8 or more weeks compared with 13.2% in the placebo arm. In the BELIEVE trial, 21.4% of patients in the luspatercept arm achieved a 33% or higher reduction in transfusion burden, with a reduction of 2 or more RBC units, during weeks 13 to 24, when compared with a 12-week baseline period versus 4.5% of those on placebo. Specifically, 19.6% patients on luspatercept achieved a 33% or higher reduction in RBC transfusion burden at weeks 37 to 48 compared with 3.6% of those receiving placebo.

***********************************

A biologics license application has been resubmitted to the FDA for the pegfilgrastim biosimilar LA-EP2006 to decrease the incidence of infection from febrile neutropenia in patients with nonmyeloid malignancies who are receiving myelosuppressive anticancer therapy. The resubmission addresses a complete response letter the FDA issued in June 2016.

With the resubmission, the application includes new data from a pivotal single-dose, three-period, cross-over, pharmacokinetics and pharmacodynamics study comparing Sandoz’s pegfilgrastim biosimilar with US-sourced reference pegfilgrastim; the pegfilgrastim biosimilar with European Union–sourced reference pegfilgrastim; and US- with EU-sourced reference pegfilgrastim.

At the time of the 2016 CRL, Sandoz had stated that it was working with the FDA to address remaining questions.

Investigators from the phase I trial noted that due to historically known high intra- and inter-subject variabilities with reference biologic in area under the serum concentration-time curve, the study is appropriate and establishes the scientific bridge to demonstrate similarity of PK/PD, safety, and immunogenicity between LA-EP2006, EU reference pegfilgrastim, and US reference pegfilgrastim. As of October 2018, the trial was ongoing in 1 Dutch and 5 US study sites.

The European Commission approved LA-EP2006, known by the trade name Ziextenzo, as a treatment to reduce the duration of neutropenia and incidence of febrile neutropenia that is associated with anticancer chemotherapy in November 2018.

*********************************

In breast cancer, the European Commission has approved olaparib for the treatment of adult patients with germline BRCA1/2-mutant, HER2-negative locally advanced or metastatic disease.

The decision is based on findings from the phase III OlympiAD trial, in which the PARP inhibitor reduced the risk of disease progression or death by 42% compared with chemotherapy in patients with germline BRCA-mutant, metastatic disease.

With the indication, patients must have been previously treated with an anthracycline and a taxane in the neoadjuvant or metastatic setting unless they were ineligible to receive them. Additionally, those with hormone receptor—positive breast cancer must have progressed on or following endocrine therapy or be ineligible for the treatment.

In OlympiAD, results showed that the median progression-free survival was 7.0 months with olaparib versus 4.2 months with chemotherapy, demonstrating a statistically significant improvement.

Additionally, the overall response rates were 52% and 23% for olaparib and chemotherapy, respectively. The median duration of response was 6.4 months in the olaparib group and 7.1 months in the standard-therapy arm, and the median time to onset of response was 47 days and 45 days, respectively.

The FDA approved olaparib for this indication in January 2018.

*********************************

New evidence-based guidance statements issued by the American College of Physicians announced that women at average risk for breast cancer who are between the ages of 40 and 49 years, clinicians should have a personalized approach on whether their patients should be screened with mammography prior to the age of 50.

Additionally, the guidance statement reads that those who are at average risk for breast cancer and are between the ages of 50 and 74 with no symptoms of disease should be screened with mammography bi-annually.

These guidance statements do not apply to patients who have had prior abnormal screening results or in higher-risk patients. This includes patients with a personal history of breast cancer, or those who may harbor genetic mutations that are associated with increased risk, such as BRCA1/2 or another familial breast cancer syndrome.

Two additional guidance statements by the ACP state that for women who are at average risk for breast cancer and are 75 years or older, or in women who have a life expectancy of less than10 years, breast cancer screening should be discontinued. Moreover, in average-risk women of all ages, a clinical breast examination should not be used as a method to screen for breast cancer.

Approximately 20% of women diagnosed with breast cancer throughout a 10-year period will be overdiagnosed and likely overtreated. Harms associated with breast cancer screening include overdiagnosis; false-positive results; overtreatment; radiation exposure, as well as radiation associated breast cancers and breast cancer deaths; and anxiety and distress from the corresponding tests and procedures, which include breast biopsies.

*********************************

This week, we sat down with Drs John Marshall, of Georgetown-Lombardi Comprehensive Cancer Center, and Drs Tanios S. Bekaii-Saab, of Mayo Clinic, to discuss dosing strategies and patient support in metastatic colorectal cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
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