Multiple myeloma (cancer type) diagnosis medical concept on tablet screen with stethoscope.

Results from an overall survival (OS) analysis of the Phase III head-to-head ENDEAVOR trial were published online first in The Lancet Oncology.[1]

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.[2] It is a rare and very aggressive disease that accounts for approximately one percent of all cancers.[3][4] In the U.S., there are nearly 95,000 people living with, or in remission from, multiple myeloma.[5] Approximately 30,330 Americans are diagnosed with multiple myeloma each year and 12,650 patient deaths are reported on an annual basis.[5]

Trial data
The data showed that carfilzomib (Kyprolis?; Amgen) at 56 mg/m2 twice weekly and dexamethasone (Kd56) reduced the risk of death by 21% over bortezomib (Velcade?; Takeda Oncology) and dexamethasone, resulting in a 7.6 month OS benefit (median OS 47.6 months for Kd56 versus 40.0 for dexamethasone, HR=0.79; p=0.01). The OS benefit was consistent regardless of prior Velcade therapy (HR=0.75 for no prior bortezomib; HR=0.84 for prior bortezomib). This Kd56 regimen is already approved in the U.S., European Union and other countries based on the primary analysis of Progression-Free Survival (PFS) in the ENDEAVOR study.

?These results showed carfilzomib and dexamethasone significantly reduced the risk of death compared to bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma,? said study co-author and investigator Meletios A. Dimopoulos, M.D., professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine.

?These results support the use of carfilzomib and dexamethasone as a standard-of-care for multiple myeloma patients at first relapse,? Meletios added.

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Role of proteasomes
Proteasomes play an important role< in cell function and growth by breaking down proteins that are damaged or no longer needed.[6] Carfilzomib has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.[6] In some cells, carfilzomib can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.[6][7]

Limited results
?In recent years, few clinical trials have demonstrated overall survival benefits in patients with relapsed or refractory multiple myeloma,? noted Sean E. Harper, M.D., executive vice president of Research and Development at Amgen.

?In ENDEAVOR, the only head-to-head trial comparing proteasome inhibitors, carfilzomib showed a statistically significant overall survival benefit of 7.6 months over bortezomib. These results published today in The Lancet Oncology support carfilzomib as a superior proteasome inhibitor in relapsed multiple myeloma patients. We?ve shared these data with regulatory agencies in the U.S. and Europe to support a potential label update,? Harper further noted.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. Notably, rates of grade 2 or higher peripheral neuropathy, a frequent dose-limiting toxicity of bortezomib, were five-times lower in patients receiving Kd56 versus patients receiving dexamethasone (7% versus 35%, respectively). The most common adverse events (greater than or equal to 20%) in the carfilzomib arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

As previously published in The Lancet Oncology, patients treated with Kd56 also achieved PFS of 18.7 months compared to 9.4 months in those receiving dexamethasone, meeting the primary endpoint of the study (HR=0.53; 95 percent CI: 0.44 ? 0.65; p<0.0001).

Clinical trial program
Since its approval in 2012, carfilzomib has been prescribed to over 50,000 patients worldwide. The carfilzomib clinical program continues to focus on providing solutions for physicians and patients in treating this frequently relapsing and difficult-to-treat cancer. Carfilzomib is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

Carfilzomib is approved in the U.S. in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Last editorial review: August 23, 2017

Featured Image: Multiple Myeloma. Courtesy: ? 2017 Fotolia . Used with permission.

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