By a News Reporter-Staff News Editor at Pharma Business Week Bristol-Myers Squibb Company (NYSE:BMY) announced the U.S. Food and Drug Administration (FDA) has expanded the indication for Sprycel (dasatinib) tablets to include the treatment of pediatric patients one year of age and older with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in combination with chemotherapy.1 Sprycel is the only second-generation tyrosine kinase inhibitor approved for this patient population. The approval, which was granted following priority review by the FDA, is based on data from the Phase 2 study, CA180-372 (NCT01460160) (see also Bristol-Myers Squibb).
"We recognize the urgency around developing and delivering therapies for children and young adults living with cancer, and today's approval is an important example of our commitment to pediatric oncology," said Jeffrey Jackson, Ph.D., development lead, hematology, Bristol-Myers Squibb. "Building on our previous indication for children with Ph+ chronic myeloid leukemia in chronic phase, we're pleased to bring Sprycel tablets to a second type of pediatric leukemia. This approval will give physicians another treatment option to offer appropriate pediatric patients with Ph+ ALL." Sprycel is associated with the following Warnings and Precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity and effects on growth and development in pediatric patients.1 Please see detailed Important Safety Information below. The efficacy of Sprycel tablets in combination with chemotherapy was evaluated in a single cohort of the Phase 2, multicenter, single-arm CA180-372 study, which included 78 pediatric patients with newly diagnosed B-cell precursor Ph+ ALL.1,2 At three years, the study demonstrated an event-free survival (EFS) binary rate of 64.1% (95% confidence interval [CI]: 52.4 to 74.7).1 Event-free survival is defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.
Of the 81 patients evaluated for safety, fatal adverse reactions occurred in three patients (4%), and eight (10%) experienced adverse reactions leading to treatment discontinuation, including fungal sepsis, hepatotoxicity of graft versus host disease, thrombocytopenia, CMV infection, pneumonia, nausea, enteritis and drug hypersensitivity.1 The most common serious adverse reactions (incidence =10%) were pyrexia, febrile neutropenia, mucositis, diarrhea, sepsis, hypotension, infections (bacterial, viral and fungal), hypersensitivity, vomiting, renal insufficiency, abdominal pain and musculoskeletal pain.1 "As treatments have advanced in recent years, we've seen improvements in outcomes for pediatric patients with Ph+ ALL overall, but there remains a need for additional options,"3 said Stephen Hunger, MD, lead study author, chief of the division of oncology and director of the Center for Childhood Cancer Research at Children's Hospital of Philadelphia. "The Phase 2 CA180-372 trial was particularly informative because it was designed to limit the use of cranial irradiation and stem cell transplant. In the study, Sprycel plus chemotherapy demonstrated a three-year event-free survival benefit. These results show that Sprycel is an effective medication for physicians to consider for children and adolescents with Ph+ ALL."1,4 Acute lymphoblastic leukemia is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells.5 The most common childhood cancer in the United States, ALL represents 20% of all cancers diagnosed in persons aged less than 20 years, or more than 3,000 new cases each year.6 Three percent of children who have ALL have the Ph+ subtype, which means they have a chromosome alteration that results in a specific mutation of the BCR-ABL gene.3 "Coping with a pediatric cancer diagnosis, including searching for and identifying the right treatment regimen, can take a physical and emotional toll on patients and their families," said Vickie Buenger, president of the Coalition Against Childhood Cancer (CAC2). "The availability of another option is a welcome step forward for those affected by this disease."
In addition to this pediatric approval, Sprycel is approved for use in children one year of age and older with Ph+ chronic myeloid leukemia (CML) in chronic phase (CP).1 About the Phase 2 CA180-372 Study In the CA180-372 trial, the 78 patients evaluated for efficacy in cohort 1 received Sprycel at a daily dose of 60 mg/m2 for up to 24 months, in combination with chemotherapy.1 The backbone chemotherapy regimen was the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol.1 Efficacy was established based on three-year EFS, defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.1 The trial was designed such that patients with central nervous system 3 disease receive cranial irradiation.4 Patients were assigned to receive stem cell transplant (SCT) based on minimal residual disease if they were considered high-risk.4 Data from the CA180-372 trial were presented at the 2017 American Society of Hematology Annual Meeting.
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