Advanced Melanoma Patients with Initial BRAF Therapy Resistance Can Be Treated Again, Study Finds

Advanced Melanoma Patients with Initial BRAF Therapy Resistance Can Be Treated Again, Study Finds

People with advanced and metastatic melanoma who had become resistant to BRAF-targeted therapy were successfully retreated with this therapy after a three-month pause, researchers in Belgium reported.

A liquid biopsy tool, Idylla ctBRAF Mutation Assay, developed by Biocartis, was used to monitor patients’ mutational status. The non-invasive biopsy assay detects tumor DNA circulating in the blood.

The study, “Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial,” was led by Bart Neyns from the University Hospital Brussels, and published in The Lancet Oncology.

Patients with BRAFV600-mutant melanoma benefit from a treatment that combines BRAF and MEK inhibitors, but resistance and disease progression eventually develops in most.  However, preclinical studies and case studies have indicated that acquired resistance to BRAF inhibition may be reversible, and the researchers decided to challenge a tumor again with these inhibitors to see if the treatment might be effective in certain patients.

The team conducted a prospective Phase 2 clinical trial (NCT02296996), assessing the anti-tumor activity of retreatment in 25 patients with advanced BRAFV600-mutant melanoma, whose disease progressed after treatment with BRAF plus MEK inhibitors (Tafinlar plus Mekinist). All had stopped the therapy for at least 12 weeks. These patients were then given  Tafinlar (dabrafenib) 150 mg orally twice per day and Mekinist (trametinib) 2 mg orally once per day.

Researchers assessed the number of patients showing a complete or partial response to retreatment, the study’s primary endpoint, using the Response Evaluation Criteria in Solid Tumors (RECIST).

The results showed that eight people achieved a partial response, and stable disease was noted in 10 patients. Retreatment was well-tolerated, with no major adverse events; however, one patient had inflammation of subcutaneous adipose tissue (panniculitis), and another experienced fever.

Based on the anti-tumor activity seen, the team concluded that retreatment is a potential new therapy option for patients with advanced metastatic melanoma cancer who had previously progressed on BRAF inhibitors.

“This is an important finding, as these results show that we can restart treatment with reasonable chance of success in cases where we do not have an effective standard treatment,” Bart Neyns, head of medical oncology at the University Hospital Brussels (Belgium), said in a news release.

“The study … shows for the first time that interruption after progression can restore sensitivity to a targeted therapy,” said Geert Maertens, chief scientific officer of Biocartis, and that the assay can be  “instrumental in identifying patients benefiting from such retreatment,” allowing for “high precision patient management.”

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