Real-world outcomes of combined lenvatinib and anti-PD-1 in advanced melanoma: Lenvamel, a multicenter retrospective study of the French Group of Skin Cancers.

9546 Background: Treatment options for patients (pts) with advanced melanoma who experience resistance to immunotherapy (ICI) +- targeted therapy are lacking. Studies suggest the anti-tumour activity of combined pembrolizumab and lenvatinib in pts progressing on ICI. We report the clinical outcomes of combined lenvatinib and anti-PD-1 in this population. Methods: This French multicenter real-world study was conducted from 09/2020 to 07/2023. The primary endpoint was objective response rate (ORR) according to the RECIST criteria (v.1.1). Secondary endpoints were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS) and duration of response (DOR). Results: Of the 67 pts included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV M1c or M1d disease. Baseline characteristics are presented (Table). Overall ORR was 28.4% (95%CI, 18–41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. ORR was 71.4% (95%CI, 29–96%) for mucosal melanoma, 32,8% (95%CI, 21–46%) for pts pre-treated with anti-PD-1 + anti-CTLA-4, and 31,5% (95%CI, 20–46%) for BRAF wild-type melanoma. Median DOR was 3.1 (IQR, 1.3–4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5–3.7) and 9.8 (95% CI, 5.6–13.9) months respectively. Grade 3–4 TRAEs occurred in 16 pts (24%, no grade 5); common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). Conclusions: Our study demonstrates an interesting response rate and acceptable safety profile of this combination, with manageable toxicities, in an immuno-refractory population with poor prognostic factors. Pts pre-treated with anti-PD-1+ anti-CTLA-4, and those with BRAF wild-type melanoma seemed to benefit more from this strategy. Our study also provides promising data (considering the small sample) for pts with mucosal melanoma. Our data support this treatment option for refractory melanoma, though not yet approved by the health authorities, and highlight the need for new strategies. Table: see text