# Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy

## TL;DR

Switching from PD-1 to BRAF + MEK therapy after melanoma recurrence improves recurrence-free survival compared to the reverse switch.

## Contribution

Demonstrates that switching from PD-1 to BRAF + MEK adjuvant therapy after recurrence provides better recurrence-free survival than switching in the opposite direction.

## Key findings

- BRAF + MEK therapy showed superior 12- and 24-month recurrence-free survival compared to PD-1 therapy in second-course adjuvant treatment.
- Switching from PD-1 to BRAF + MEK treatment provided better overall recurrence-free survival than switching from BRAF + MEK to PD-1.
- Both treatment approaches showed high 24-month overall survival rates with no new safety signals detected.

## Abstract

PD‐1 or BRAF + MEK inhibition is considered the current gold standard in adjuvant melanoma therapy. Little is known if, after the recurrence of the disease and surgery, a second course of adjuvant therapy might be beneficial.

A multicenter, retrospective study investigating a second course of adjuvant therapy after recurrence and surgery in stage III–IV melanoma patients. Patients received nivolumab (NIV), pembrolizumab (PEM) or dabrafenib plus trametinib (D + T) between 01/2017 and 10/2021. The primary endpoint was 12‐month recurrence‐free survival (RFS2). Further analyses included descriptive and correlative statistics.

Sixty‐six patients from 22 centers in Germany, Austria and Switzerland were included. Thirty‐two patients received D + T as second‐course adjuvant therapy, 9 patients received PEM and 25 patients received NIV. Recurrence‐free survival for the second‐course adjuvant treatment (RFS2) was assessed after 12 and 24 months and showed a superiority of adjuvant BRAF + MEK over PD‐1 therapy (12‐months RFS2: 90.6% vs. 70.6%, HR 4.226 [95% CI 1.154–15.48]; p = 0.030; 24‐months RFS2 71.9% vs. 52.9%, HR 3.154 [95% CI 1.374–7.242]; p = 0.007). There was no significant decrease in OS with either BRAF + MEK or PD‐1 treatment (12‐months OS: 100% both, 24‐months OS: 100% vs. 93.8%).

Furthermore, therapy sequences were investigated. For better comparability, only BRAF V600 mutated patients were assessed: RFS2 was significantly better for patients with a class switch from PD‐1 to BRAF + MEK compared to BRAF + MEK to PD‐1 (HR 4.401 (1.04–18.63), p = 0.044). No new safety signals were detected.

In the investigated cohort, a second course of adjuvant melanoma treatment is feasible and provides similar RFS compared to an initial course of adjuvant therapy using BRAF + MEK inhibitors; however, RFS2 is reduced for PD‐1 antibodies. In addition, both treatments were convincing with a 24‐month OS of almost 100%. Switching from adjuvant PD‐1 to BRAF + MEK treatment provided better overall RFS compared to switching from adjuvant BRAF + MEK to PD‐1 treatment.

66 patients from 22 centers received adjuvant treatment after relapse under or after previous adjuvant therapy with BRAF + MEK or PD‐1. Data highlight a significant benefit when switching from PD‐1 to BRAF + MEK adjuvant therapy compared to a switch from BRAF + MEK to PD‐1 adjuvant regimens.