FDA Approves BOSULIF® for Newly Diagnosed Chronic Myeloid Leukemia

December 28th, 2017

SUMMARY: The FDA on December 19, 2017 granted accelerated approval to BOSULIF® (Bosutinib) for treatment of patients with newly diagnosed Chronic Phase Philadelphia chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML). Chronic Myeloid Leukemia (CML) constitutes a little over 10% of all new cases of leukemia. The American Cancer Society estimates that about 8,950 new CML cases will be diagnosed in the United States in 2017 and about 1,080 patients will die of the disease. The hallmark of CML, the Philadelphia Chromosome (Chromosome 22), is a result of a reciprocal translocation between chromosomes 9 and 22, wherein the ABL gene from chromosome 9 fuses with the BCR gene on chromosome 22. As a result, the auto inhibitory function of the ABL gene is lost and the BCR-ABL fusion gene is activated resulting in cell proliferation and leukemic transformation of hematopoietic stem cells. The presently available Tyrosine Kinase Inhibitors (TKI’s) approved in the United States including GLEEVEC® (Imatinib), share the same therapeutic target, which is BCR-ABL kinase. BOSULIF® is a potent, dual Abl and Src tyrosine kinase inhibitor and was approved by the FDA in 2012 for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML) with resistance or intolerance to prior therapy.

Monitoring MMR in CMLThis new approval for BOSULIF® was based on the efficacy and safety data from BFORE trial, which is an ongoing randomized, open-label, multicenter, phase III study in which in 487 patients with Ph+ newly diagnosed Chronic Phase CML were randomized to receive either BOSULIF® 400 mg once daily (N=246) or GLEEVEC® (Imatinib) 400 mg once daily (N=241). The median age of patients was 53 years, the Sokal risk group was intermediate and high for 40% and 21% of patients, respectively, and over two thirds of the patients had an ECOG PS score of 0. Sokal score is calculated using a formula that includes Age, Spleen size, Platelet count and percentage of Myeloblasts and has three risk groups: Low-risk (Sokal score<0.8), Intermediate-risk (Sokal score 0.8-1.2) and High-risk (Sokal score >1.2). The Primary endpoint was Major Molecular Response (MMR) at 12 months, defined as BCR-ABL ratio on International Scale of 0.1% or less, which corresponded to 3 or more log reduction from standardized baseline.

After 12 or more months of follow up, the MMR at 12 months was 47.2% in the BOSULIF® group and 36.9% in the GLEEVEC® group (P=0.02) and the time to achieve a MMR was shorter in the BOSULIF® group (P<0.02). The Complete Cytogenetic Response (CCyR) at 12 months was also significantly higher with BOSULIF® versus GLEEVEC® (77.2% vs 66.4%; P< 0.008), with the time to achieve a CCyR, shorter for BOSULIF® (P<0.001). The most common adverse reactions in the BOSULIF® group included rash, nausea, diarrhea, abdominal discomfort, thrombocytopenia, increased ALT and AST levels.

It was concluded that BOSULIF® is an important and useful treatment option for patient with newly diagnosed Chronic Phase CML. Bosutinib (BOS) versus imatinib (IM) for newly diagnosed chronic myeloid leukemia (CML): Initial results from the BFORE trial. Cortes JE, Gambacorti-Passerini C, Deininger MWN, et al. J Clin Oncol. 2017;35 (suppl; abstr 7002).


Hormonal Contraception Increases Breast Cancer Risk

December 28th, 2017

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. It is estimated that 252,710 new cases of invasive breast cancer and 63,410 new cases of non-invasive breast cancer will be diagnosed in women in 2017 and 40,610 women are expected to die from the disease. It is estimated that approximately 140 million women worldwide use hormonal contraception and this number accounts for approximately 13% of women between the ages of 15 and 49 years. The use of hormonal contraception has been on the rise.

Estrogen promotes the development of breast cancer. Previous published studies had shown positive associations between the use of oral contraceptives and breast cancer risk, but the results have been inconsistent from no increase in risk to a 20-30% increase in risk. Further, unlike contemporary hormonal contraception, oral contraceptives in the past contained a higher estrogen dose in the combined estrogen/progestin hormonal contraceptives, and the higher dose of estrogen has been implicated in the development of breast cancer. Contemporary products with new progestins and new routes of delivery (intrauterine system, contraceptive patches, vaginal rings, progestin-only implants, and injections) has raised new concerns, with some studies suggesting that the addition of progestin appears to increase the risk of breast cancer among postmenopausal women who receive hormone therapy. There is evidence to suggest that use of hormonal contraception at a young age may confer a higher risk of breast cancer than initiation of use later in life.

This Danish study, using their national registry, reported the risk of invasive breast cancer risk among women of reproductive age, who were using currently available hormonal contraception. This prospective cohort study conducted in Denmark included 1.8 million women between 15-49 years of age, who did not have a diagnosis of cancer or venous thromboembolism, and who had not received treatment for infertility. Individually updated information about the use of hormonal contraception, breast cancer diagnoses, and potential contributing factors, was obtained from nationwide registries.

It was noted that when compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (20% higher than average). This risk increased from 1.09 (9% higher than average) with less than 1 year of use to 1.38 (38% higher than average) with more than 10 years of hormonal contraception use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer continued to be higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives, with a relative risk of 1.21 (21% higher than average). Outcomes in this study however, could not be adjusted for age at menarche, breast feeding, alcohol consumption, physical activity or Body Mass Index.

It was concluded from this large study population that, the risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use. Additionally, these results unequivocally suggest that no hormonal contraceptives are free of risk. Contemporary Hormonal Contraception and the Risk of Breast Cancer. Mørch LS, Skovlund CW, Hannaford PC, et al. N Engl J Med 2017; 377:2228-2239


Hormonal Contraception Increases Breast Cancer Risk

December 28th, 2017

It is estimated that approximately 140 million women worldwide use hormonal contraception and this number accounts for approximately 13% of women between the ages of 15 and 49 years. Estrogen promotes the development of breast cancer and there is evidence to suggest that use of hormonal contraception at a young age may confer a higher risk of breast cancer than initiation of use later in life.
In a recent study (N Engl J Med 2017; 377:2228-2239), it was noted that the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (20% higher than average). This risk increased from 1.09 (9% higher than average) with less than 1 year of use to 1.38 (38% higher than average) with more than 10 years of hormonal contraception use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer continued to be higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives, with a relative risk of 1.21 (21% higher than average). These findings unequivocally suggest that no hormonal contraceptives are free of risk.


TASIGNA® (Nilotinib)

December 27th, 2017

The FDA on December 22, 2017 updated the product label for TASIGNA® to include information on TASIGNA® discontinuation, post-discontinuation monitoring criteria, and guidance for treatment re-initiation in patients taking TASIGNA® for Philadelphia chromosome positive (Ph+) Chronic Myeloid Leukemia (CML) who have achieved a sustained Molecular Response (MR 4.5). TASIGNA® is a product of Novartis Pharmaceuticals Corp.


SIKLOS® (Hydroxyurea)

December 27th, 2017

The FDA on December 21, 2017 granted regular approval to SIKLOS® to reduce the frequency of painful crises and the need for blood transfusions in pediatric patients from 2 years of age and older with sickle cell anemia with recurrent moderate to severe painful crises. SIKLOS® is a product of Addmedica.


PERJETA® (Pertuzumab)

December 27th, 2017

The FDA on December 20, 2017 granted regular approval to PERJETA® for use in combination with Trastuzumab and chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. PERJETA® is a product of Genentech, Inc.


OPDIVO® (Nivolumab)

December 27th, 2017

The FDA on December 20, 2017 granted regular approval to the anti-PD1 monoclonal antibody OPDIVO® for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or in patients with metastatic disease who have undergone complete resection. OPDIVO® was previously approved for the treatment of patients with unresectable or metastatic melanoma. OPDIVO® is a product of Bristol-Myers Squibb Company.


OGIVRI® (Trastuzumab-dkst)

December 27th, 2017

The FDA on December 1, 2017 approved OGIVRI® as a Biosimilar to HERCEPTIN® (Trastuzumab, Genentech, Inc.) for the treatment of patients with HER2-overexpressing breast or metastatic stomach cancer (Gastric or GastroEsophageal junction adenocarcinoma). OGIVRI® is a product of Mylan N.V.


CABOMETYX® (Cabozantinib)

December 27th, 2017

The FDA on December 19, 2017 granted regular approval to CABOMETYX® for treatment of patients with advanced Renal Cell Carcinoma (RCC). CABOMETYX® is a product of Exelixis, Inc.


BOSULIF® (Bosutinib)

December 27th, 2017

The FDA on December 19, 2017 granted accelerated approval to BOSULIF® for treatment of patients with newly-diagnosed Chronic Phase (CP) Philadelphia chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML). BOSULIF® is a product of Pfizer Inc.