How should patients responding to BRAF inhibitors be monitored?

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

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 QTcprolongation 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