In a nutshell
The authors aimed to determine the safety profile of vemurafenib in patients with BRAFV600 mutated metastatic melanoma with few treatment options remaining.
Some background
BRAF (protein in the body that controls cell growth) mutations are one of the key factors that lead to melanoma development. In particular, BRAFV600 (a type of BRAF mutation) is found in more than 50% of tumors. When BRAF is mutated (normal function is changed or prevented) it can help cancer cells avoid death and allow uncontrolled cancer cell growth.
Vemurafenib (Zelboraf) is a drug used as a treatment in metastatic melanoma (cancer has spread around the body) that prevents BRAFV600 from functioning and kills the cancer cells. It can only be used in patients that have BRAFV600 mutations. The safety of vemurafenib has been validated in studies with adverse events (undesired reaction to medication or treatment) ranging from grade 1 or 2 (minor or moderate reactions e.g. rash, fatigue, nausea) to grade 3 or 4 (severe or life-threatening e.g. cutaneous squamous cell carcinoma (lesions that need surgery in advanced melanoma)) in some patients.
Methods & findings
The aim of this study was to determine whether vemurafenib was a safe treatment option for patients with BRAFV600 mutated melanoma and unsatisfactory treatment options.
3,222 patients in this study received at least one dose of vemurafenib. The average treatment time was 5.6 months and follow-up time was 11.5 months. At the end of the study 73% had withdrawn mainly due to disease progression and 27% remained on vemurafenib treatment.
In total, 95% experienced at least one adverse event, with 87% receiving treatment for this event. 93% of patients experienced grade 1 or 2 adverse events (for example, fatigue, hair loss, nausea, joint pain). 46% of patients experienced grade 3 or 4 adverse events (for example 12% developed another form of skin cancer, 5% experienced liver function abnormalities, 5% experienced rash, 3% experienced joint pain) on average 1.7 months after treatment with vemurafenib. 1,398 of 1,480 patients (94%) experienced grade 3 or 4 events before cancer progression.
Patients over the age of 75 years were more susceptible to serious adverse events; grade 3 events in over 75 years were 59% compared to 43% of those under 75 and grade 4 events in over 75 years were 4% compared to 3% in those under 75.
87 patients died from adverse events where 20 deaths were contributed to adverse events caused by vemurafenib.
The bottom line
The authors conclude that vemurafenib is safe to use in a diverse population of BRAFV600 mutated metastatic melanoma patients.
The fine print
Not all patients completed follow-up and results were interpreted by the investigator are prone to bias.
What’s next?
If you are considering vemurafenib as a treatment option for metastatic melanoma please consult your doctor.
Published By :
Lancet oncology
Date :
Feb 26, 2014
