Most Read Articles
01 Oct 2013

Heart disease is still New Zealand’s biggest killer, with one Kiwi dying from coronary heart disease every 90 minutes. Pharmacy Today New Zealand looks at how pharmacists can help

Dr. James Salisi, 01 Jul 2014

The recent spike in the number of new cases of human immunodeficiency virus (HIV) infection in the Philippines means that clinicians and pharmacists alike may need to increase their awareness and competency in prescribing and monitoring HIV treatment. Although taught in medical and pharmacy schools, the scarcity in exposure to clinical cases before highlights the need to for physicians and pharmacist to review HIV pharmacotherapy in order to cater to the increasing HIV patient population.

01 Sep 2017
Complementary medicines can play an important part in maintaining wellness, preventing deficiencies and optimizing health outcomes, says Dr Lesley Braun PhD, Director of the Blackmores Institute. 
Audrey Abella, 16 Oct 2017
The use of angiotensin converting enzyme (ACE) inhibitors may prevent repeat revascularization in patients who underwent percutaneous transluminal angioplasty (PTA) for peripheral artery disease (PAD) compared with angiotensin receptor blockers (ARB), according to a presentation at APCH 2017.

Adjuvant BRAF and MEK inhibition reduces recurrence in stage III BRAF-mutant melanoma

Jackey Suen
18 Sep 2017
Dr Karl Lewis (left), Prof Axel Hauschild (right)

The risk of recurrence in patients with resected stage III BRAF-mutant melanoma can be reduced with adjuvant BRAF inhibitor and/or MEK inhibitor therapy, according to two phase III studies presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain.

The combination of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib was investigated in the COMBI-AD study. [ESMO 2017, abstract LBA6_PR; N Engl J Med 2017, doi: 10.1056/NEJMoa1708539]

“There has been no standard of care for adjuvant treatment of stage III melanoma,” said investigator Professor Axel Hauschild of the University of Kiel, Kiel, Germany. “Interferon is approved for this situation but its benefit is modest, providing only 20 percent improvement in relapse-free survival [RFS] compared with placebo.”

In the COMBI-AD study, 870 patients with stage III resected BRAFV600E/K mutation-positive melanoma were randomized to receive the combination of dabrafenib 150 mg BID plus trametinib 2 mg QD, or two matched placebos.

After a median follow-up of 2.8 years, the primary endpoint of median RFS was significantly longer in the combination arm vs placebo arm (not reached vs 16.6 months; hazard ratio [HR], 0.47; p<0.001). Rates of 1-year, 2-year and 3-year RFS were 88 vs 56 percent, 67 vs 44 percent and 59 vs 39 percent, respectively.

The combination therapy also improved overall survival by 43 percent vs placebo (HR, 0.57; p=0.0006).

“Forty-one percent of patients receiving dabrafenib plus trametinib had grade 3/4 adverse events [AEs], and 26 percent discontinued treatment due to AEs,” reported Hauschild. “The most common grade 3/4 AEs in patients receiving the combination therapy were pyrexia [5 percent] and fatigue [4 percent].”

“This is the first randomized study of targeted therapies for adjuvant treatment of stage III melanoma,” he added. “Our findings suggest that dabrafenib plus trametinib is an effective adjuvant treatment option for BRAFV600E/K mutation-positive melanoma.”

Meanwhile, the BRIM8 study showed that the BRAF inhibitor vemurafenib improved disease-free survival (DFS) in patients with resected BRAFV600 mutation-positive melanoma in the adjuvant setting. [ESMO 2017, abstract LBA7_PR]

“Vemurafenib has previously demonstrated meaningful clinical activity against advanced or metastatic BRAFV600 mutation-positive melanoma,” explained investigator Dr Karl Lewis of the University of Colorado Comprehensive Cancer Center, Colorado, US.

In the study, 314 patients with stage IIC–IIIB disease and 184 patients with stage IIIC disease were randomized to receive vemurafenib 960 mg BID or placebo for 1 year.

“Vemurafenib treatment led to significant improvement in the primary endpoint of DFS in patients with stage IIC–IIIB disease, but not in those with stage IIIC disease,” reported Lewis. “In patients with stage IIC–IIIB disease, median DFS was not reached in those who received vemurafenib vs 36.9 months in those who received placebo [HR, 0.54; p=0.001]. In patients with stage IIIC disease, however, the DFS benefit with vemurafenib did not reach statistical significance [median, 23.1 vs 15.4 months; HR, 0.80; p=0.2598].”

“The secondary endpoint of distant metastasis-free survival was consistent with the primary endpoint in both patients with stage IIC–IIIB disease and stage IIIC,” he added. “The safety profile of vemurafenib was similar to that previously reported in clinical studies.”

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Most Read Articles
01 Oct 2013

Heart disease is still New Zealand’s biggest killer, with one Kiwi dying from coronary heart disease every 90 minutes. Pharmacy Today New Zealand looks at how pharmacists can help

Dr. James Salisi, 01 Jul 2014

The recent spike in the number of new cases of human immunodeficiency virus (HIV) infection in the Philippines means that clinicians and pharmacists alike may need to increase their awareness and competency in prescribing and monitoring HIV treatment. Although taught in medical and pharmacy schools, the scarcity in exposure to clinical cases before highlights the need to for physicians and pharmacist to review HIV pharmacotherapy in order to cater to the increasing HIV patient population.

01 Sep 2017
Complementary medicines can play an important part in maintaining wellness, preventing deficiencies and optimizing health outcomes, says Dr Lesley Braun PhD, Director of the Blackmores Institute. 
Audrey Abella, 16 Oct 2017
The use of angiotensin converting enzyme (ACE) inhibitors may prevent repeat revascularization in patients who underwent percutaneous transluminal angioplasty (PTA) for peripheral artery disease (PAD) compared with angiotensin receptor blockers (ARB), according to a presentation at APCH 2017.