Should Targeted Therapy Be Continued in BRAF-Mutant Melanoma Patients after Complete Remission?

BACKGROUND

Targeted therapy is used to treat patients with a BRAF-mutated metastatic melanoma and is continued until disease progression or severe toxicity. No robust data on the management of patients achieving a complete remission (CR) are available.

MAIN OBJECTIVE

To determine the relapse rate in the first year after targeted therapy discontinuation in patients in CR.

SECONDARY OBJECTIVES

To determine the relapse rates throughout the follow-up and to identify prognostic factors for relapse at 1 year.

METHODS

A retrospective, monocentric observational study was conducted in patients with advanced melanoma included in the RIC-Mel database who discontinued targeted therapy after achieving a CR confirmed by CT scan and PET/CT scan.

RESULTS

Twenty-nine patients were included. Seventeen (58.6%) patients were treated with BRAF inhibitor (BRAFi) alone and 12 (41.4%) with a BRAFi combined with a MEK inhibitor (BRAFi + MEKi). The median treatment duration was 9.7 months. The relapse rates after discontinuation were 69% at 12 months (BRAFi: 70.6%; BRAFi + MEKi: 66.7%) and 76% at 36 months (BRAFi: 76.5%; BRAFi + MEKi: 75%). A non-significant trend towards a higher risk of relapse was found in women (p = 0.1; RR 3.36; 95% CI 0.77-17.07), in patients with an LDH level greater than the upper limits of normal (p = 0.58; RR 2.43; 95% CI 0.10-56.71), and when more than two metastatic sites were involved (p = 0.19; RR 4.6; 95% CI 0.46-46.51). After relapse, targeted therapy was resumed in 17 patients (7 with BRAFi; 10 with BRAFi + MEKi) with a response rate of 53%.

CONCLUSIONS

This real-life study provided long-term data in patients who discontinued targeted therapy after CR. Most patients experienced a relapse in the first year after targeted therapy discontinuation, of whom 50% were in the first 3 months. After targeted therapy resumption, 53% of relapsing patients achieved an objective response. Patients should be followed during the first year after treatment discontinuation. In addition, patients with less than 3 metastatic sites, a baseline LDH level with normal ranges, men, and patients responding rapidly to treatment would be more likely to maintain a CR after treatment discontinuation.