BRAF/MEK Inhibitor Rechallenge Can Benefit Patients With Advanced Melanoma

Patients with advanced melanoma can derive a benefit from BRAF/MEK inhibitor rechallenge, according to research published in Cancer.

For this study, researchers evaluated data from 468 patients with advanced melanoma from the Dutch Melanoma Treatment Registry. Patients received their first treatment with BRAF/MEK inhibitors in the first line (74%), second line (18%), or third line (7%).

Most patients (71%) had achieved a response during their first BRAF/MEK inhibitor treatment, and 6% of patients had a complete response. The median progression-free survival (PFS) from this treatment was 6.8 months, and the median overall survival (OS) was 21.1 months.

Rechallenge was defined as BRAF/MEK inhibitor treatment received after a break of at least 30 days from the last BRAF/MEK inhibitor treatment. Most patients (76.3%) received an immune checkpoint inhibitor in the treatment line before rechallenge.

Most patients (n=324) received BRAF/MEK inhibitor rechallenge after initial BRAF/MEK inhibitor therapy, 65 patients received BRAF/MEK inhibitor therapy after initial BRAF inhibitor monotherapy, 63 received BRAF inhibitor monotherapy twice, and 16 received BRAF inhibitor monotherapy after BRAF/MEK inhibitor therapy.

The median follow‐up from the start of rechallenge was 42.6 months. The objective response rate was 43%, the complete response rate was 3%, the median PFS was 4.8 months, and the median OS was 8.2 months.

Patients had lower odds of responding to rechallenge if they stopped their first BRAF/MEK inhibitor therapy due to disease progression or if they had lactate dehydrogenase (LDH) levels that were more than twice the upper limit of normal (ULN).

Patients had an increased risk of progression or death if they stopped their first BRAF/MEK inhibitor therapy due to disease progression, had symptomatic brain metastasis, had LDH levels 1 to 2 times the ULN, or had LDH levels greater than 2 times the ULN.

Patients had an increased risk of death if they were 70 years of age or older, had ECOG scores of 2 or higher, had symptomatic brain metastasis, had LDH levels 1 to 2 times the ULN, or had LDH levels greater than 2 times the ULN. Patients had a lower risk of death if they had a prolonged treatment interval.

“The present study shows that patients can derive benefit from rechallenge,” the researchers concluded. “Future studies should focus on finding the optimal rechallenge strategy in terms of treatment interval and intermittent treatment to optimize survival after rechallenge in advanced melanoma patients.”

Disclosures: The Dutch Melanoma Treatment Registry is funded by Bristol‐Myers Squibb, Merck Sharpe & Dohme, Novartis, and Pierre Fabre. It was previously funded by Roche Pharma. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor