1. How often should they be evaluated and scanned, and how often should they have dermatologic follow-up and EKGs? How should patients responding to BRAF inhibitors be monitored?

2. Monitoring of side effects with BRAF inhibitors: Vemurafenib Vemurafenib Prescribing Information, Genentech, Inc.; 2011 QT prolongation  Do not start treatment in patients with uncorrectable electrolyte abnormalities, QTc > 500 ms, or long QT syndrome, or in patients who are taking medicinal products known to prolong the QT interval  Evaluate EKGs before treatment, 15 days after treatment initiation, monthly during the first 3 months of treatment, and every 3 months thereafter or more often as clinically indicated  Monitor EKG and electrolytes, including potassium, magnesium, and calcium, after dose modification for QTc prolongation Liver function  Monitor transaminases, alkaline phosphatase, and bilirubin before initiation of treatment and monthly during treatment, or as indicated Skin lesions  Perform dermatologic evaluations prior to initiation of therapy and every 2 months while on therapy  Manage suspicious skin lesions with excision and dermatopathologic evaluation. Consider dermatologic monitoring for 6 months following discontinuation of therapy

3. Monitoring of side effects with BRAF inhibitors: Dabrafenib Darafenib Prescribing Information, GSK; 2013 Skin lesions  Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation Hyperglycemia  Monitor serum glucose levels as clinically appropriate during treatment in patients with pre-existing diabetes or hyperglycemia  Advise patients to report symptoms of severe hyperglycemia such as excessive thirst or any increase in the volume or frequency of urination Uveitis  Monitor patients for visual signs and symptoms of uveitis (e.g., change in vision, photophobia, and eye pain) G6PD deficiency  Closely observe patients with G6PD deficiency for signs of hemolytic anemia

4. How often should disease be evaluated in BRAF inhibitor patients? In prior trials of vemurafenib, dabrafenib, or dabrafenib + trametinib combined, scans were initially every 6 weeks, then after 18 months they were stretched out to 12 weeks I personally suggest visits on treatment with laboratories and a H & P every 4 weeks for 6– 9 months, and scans every 8 weeks, then 6 week visits and 12 week scans thereafter