The EBIN study

In recent years, several studies have evaluated the optimal treatment sequence in patients with BRAF-mutated advanced melanoma. These studies concluded that immunotherapy first, followed by targeted therapy is preferred when treatments are given until disease progression. However, the potential benefit of an induction treatment with targeted therapy with dual BRAF+MEK inhibition followed by immunotherapy before disease progression is unclear. This research question was addressed in the phase II EBIN study and during ASCO 2024, Prof Dr Caroline Robert (Gustave Roussy Cancer Campus, University of Paris-Saclay, Villejuif, France) presented the primary analysis of this trial.

EBIN is an international, randomized controlled, phase II trial in which 271 patients with BRAF-mutated advanced melanoma were randomly assigned to receive upfront immunotherapy (nivolumab [nivo: 3mg/kg] + ipilimumab [ipi: 1mg/kg] q3w x4 followed by nivo 480 mg q4w) or a 3-month induction treatment with targeted therapy (encorafenib 450 mg QD + binimetinib 45 mg BID orally) followed by immunotherapy (same regimen as in the control arm).

After a median follow-up of 21 months, the progression-free survival (PFS, primary endpoint) did not differ between the two treatment arms (median PFS: 9 months in both arms; HR[95%CI]: 0.87[0.67-1.12]). Interestingly, however, a pre-specified subgroup analysis was highly suggestive for a treatment benefit with targeted therapy induction in patients with a baseline lactate dehydrogenase (LDH) level that was more than twice the upper limit of normal (ULN) (HR[95%]: 0.46[0.21-1.03]). Among patients with liver metastases at baseline, the PFS benefit induced with the targeted therapy induction proved to be statistically significant (HR[95%CI]: 0.49[0.29-0.84]). However, we must underscore that the latter was not a pre-specified analysis, reducing the statistical power of this finding.

While EBIN did not reveal a PFS difference between the two treatment strategies in unselected patients, it suggests a potential benefit of targeted therapy induction followed by immunotherapy prior to progression in patients with a very high baseline LDH level and in patients with liver metastases.