Adverse Event Management for BRAF/MEK Inhibitors in Melanoma
“Nurses are our frontline as far as giving these treatments and also in teaching our patients about side effects and detecting them,” Grace Cherry, NP, MSN, RN said.
With BRAF mutations occurring in about 50% of patients with cutaneous melanoma1, the advent of BRAF/MEK inhibitors for this disease type have drastically improved outcomes in recent years, according to Grace Cherry, NP, MSN, RN, a hematology/oncology nurse practitioner at the Ronald Regan UCLA Medical Center.
Cherry discussed recent exciting advancements in the melanoma field at the 4th Annual School of Nursing Oncology Live, Interactive Webcast.2
“BRAF is a driver mutation,” Cherry said. “It’s like a light switch that signals cells to constantly grow…When it’s switched on, there’s no stopping that signal. It’s continuing to allow those tumors to grow rapidly. So, when given a BRAF/MEK inhibitor, it’s like turning off that switch.”
There are 3 different categories of BRAF/MEK inhibitors. And while there are some overlapping adverse events (AEs) between them, such as fatigue and nausea, each regimen has common AEs that nurses need to be aware of when treating their patients, according to Cherry. In particular, she noted the following:
- dabrafenib (Tafinlar)/trametinib (Mekinist): fever
- vemurafenib (Zelboraf)/cobimetinib (Cotellic): rash and photosensitivity
- encorafeinb (Braftovi)/binimetinib (Mektovi): nausea
“Nurses are our frontline as far as giving these treatments and also in teaching our patients about side effects and detecting them,” Cherry said.
The first step in managing AEs from BRAF/MEK inhibition is confirming that patients have a BRAF V600E or BRAF V600K mutation. “If [patients] get these drugs and they’re BRAF wildtype or BRAF negative, they can have a paradoxical effect and make the tumor grow.”
Patients should then undergo a dermatological exam and an echocardiogram, since there is a small chance that they may have a cardiotoxicity. If the patient is experiencing blurred vision — which is rare – they should be sent to an ophthalmologist to check for ocular toxicity.
All patients experiencing AEs from their BRAF/MEK inhibition treatment should undergo labwork, where clinicians can monitor for elevated levels of liver enzymes, white blood cell counts, and rare AEs. Cherry also said that dose interruptions and dose reductions were very common in the clinical trials leading up to the drugs’ approvals.
“It’s warranted to do a dose reduction so [patients] can continue taking it on a continuous basis and sometimes they may discontinue if [toxicities] are really severe,” Cherry said.
Despite the landmark advances of BRAF/MEK inhibitors — as well as other agents, such as immunotherapy – in melanoma, there is still more work to be done
“Our patients have come a long way, compared to before BRAF/MEK inhibitors and immunotherapy came along, but we have a long way to go,” Cherry said. “Not everybody responds to [these agents] and we need to improve them.”
- Cheng, et. al. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Modern Pathology. 2018 Jan; 31(1) 24-38. Doi: 10.1038/modpathol.2017.104
- Cherry, G. Melanoma: Treatment Updates for 2020. Presented at: 4th Annual School of Nursing Oncology Live, Interactive Webcast. July 31-August 1, 2020.