A large group of researchers from institutions around the United States and Australia are conducting an ongoing study of a combination of an oral BRAF inhibitor (BRAFi) and an oral MEK 1/2 inhibitor for patients with BRAFi-naïve melanoma. At the upcoming meeting of the American Society of Clinical Oncology (ASCO), being held in Chicago from June 1-5, the researchers will present results from a Phase I/II study that demonstrate that the combination drug is both safe and efficacious.
The second part of this trial enrolled 125 patients with V600 BRAF mutant solid tumors; this included 77 patients with no prior BRAFi. Patients were treating on four escalating dose scales of dabrafenib/trametinib (mg BID/mg QD): 75/1, 150/1, 150/1.5, 150/2.
Among the 77 melanoma patients who had never received BRAFi, the median age was 52 years; patients were 61% male with 57% ECOG PS of 0, 91% V600E, 65% M1c stage, 26% prior brain metastases, and 52% LDH > ULN. According to the abstract of the presentation that will be given at ASCO, the “confirmed ORR was 56% (95% CI: 44.1%-67.2%) with 4 CR, 39 PR, 29 SD and 3 PD. Confirmed response rate for each dose level, respectively, was 67% (n=6), 64% (n=22), 48% (n=25) and 54% (n=24). Median PFS (months) for each dose level, respectively, was: 8.7, 8.3, 5.5; PFS is not mature for 150/2. Overall PFS was 7.4 (95% CI: 5.5-9.2).”
According to the ASCO abstract, skin toxicity greater than or equal to a Grade 2 adverse event (AE) occurred in 17 patients (14%). The most common Grade 3 and Grade 4 AEs were pyrexia (n=6, 5%), fatigue (n=6, 5%) and dehydration (n=6, 5%). Three cases of cutaneous squamous cell carcinoma were reported as well as two cases of actinic keratosis.
The researchers conclude: “The combination of dabrafenib/trametinib has an acceptable safety profile, with a lower incidence of MEKi-related rash and BRAFi-induced hyperproliferative skin lesions compared with the single agents. The clinical activity of dabrafenib/trametinib observed in pts with V600 BRAF mutant metastatic melanoma is encouraging and will be investigated further in a phase III trial.”
