Authors: Daphne Boulicault, Future Science Group
A paper published recently in the New England Journal of Medicine has revealed that a new targeted combination drug therapy significantly reduces the risk of disease progression and death in patients with metastatic melanoma.
The multicenter research team conducted a double-blind, randomized Phase III trial to compare oral trametinib (2 mg once daily) and oral dabrafenib (150 mg twice daily) combination therapy with oral dabrafenib (150 mg twice daily) and placebo.
The trial consisted of participants with inoperable stage IIIC or IV metastatic melanoma with a BRAF gene mutation V600E or V600K. Approximately 40% of patients with metastatic melanoma carry a BRAF gene mutation, which can aid in the growth and spread of melanoma tumors.
Lead author Georgina Long (University of Sydney, Australia) highlighted their results: “We show a significant 25% reduction in the risk of disease progression with the combination of dabrafenib and trametinib over single-agent dabrafenib. We also report a significant 37% relative reduction in the risk of death among people who received the combination drug therapy compared with monotherapy.”
This finding adds to the growing evidence for the efficacy of targeted combination therapies in halting disease progression and extending life expectancy for patients with cancers associated with genetic mutations that resist targeted monotherapies as well as standard chemotherapies.
Another notable result of the trial was that 67% of patients (two in three) treated with the combination therapy had a complete or partial response, while only 51% patients (one in two) achieved the same response when treated with dabrafenib montherapy.
“This means that significantly more patients who received combination therapy experienced complete or partial tumor regression compared to patients who received monotherapy,” explained Long.
“Unlike standard chemotherapy, so-called BRAF-targeted therapies are designed to interact with specific molecules that are part of the pathways and processes used by cancer cells to grow, divide, and spread in the body.”
Long emphasized the benefits of new generation targeted drug therapies over standard chemotherapies: “They’re designed to target specific vulnerabilities in the cancer cell, while most standard chemotherapies were identified through trial and error. Also, targeted therapies tend to have fewer and less toxic side effects than standard chemotherapy, because they do less damage to normal cells.”
Nonetheless, combination therapies of these drugs need to be investigated: “Trials of BRAF-targeted monotherapies reveal that half the patients start to develop resistance about six to seven months after starting therapy,” Long recognizes. “This is why researchers are conducting trials of combination therapies that target and interrupt the mechanisms that allow cancer cells to resist monotherapies.”