Real-life evidence of encorafenib plus binimetinib in patients with unresectable advanced or metastatic BRAF V600 -mutant melanoma in Spain: the BECARE (GEM-2002) trial

Ainara Soria Rivas ¹ Pedro Sanchez Mauriño ² Juan Jose Serrano Domingo ¹ Regina García Galindo ³ Silvia Sequero ⁴ Lourdes Gutiérrez Sanz ⁵ Guillermo Crespo ⁶ Roberto Díaz-Beveridge ⁷ Teresa Puértolas ⁸ Pedro López ⁹ Joaquín Fra Rodríguez ¹⁰ Rafael López Castro ¹¹ Cristina Aguayo ¹² Javier Valdivia ¹³ Alberto Jacobo Cunquero-Tomás ¹⁴ Gretel Benítez ¹⁵ Pablo Ayala De Miguel ¹⁶ Enrique Espinosa ¹⁷ Eva Muñoz Couselo ¹⁸ Begoña Campos ¹⁹ Lourdes García Sánchez ²⁰ Pablo Cerezuela-Fuentes ^21*

• ¹ Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain
• ² Medical Oncology, Hospital Universitario Reina Sofia, Córdoba, Spain
• ³ Medical Oncology, Hospital Universitario de Jerez de la Frontera, Jerez de la Frontera, Spain
• ⁴ Medical Oncology, Hospital Universitario San Cecilio, Granada, Spain
• ⁵ Medical Oncology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
• ⁶ Medical Oncology, Hospital Universitario de Burgos, Burgos, Spain
• ⁷ Medical Oncology, Hospital Universitario y Politécnico la Fe de Valencia, Valencia, Spain
• ⁸ Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Aragon, Spain
• ⁹ Medical Oncology, Complejo Hospitalario de Jaén, Jaén, Andalusia, Spain
• ¹⁰ Medical Oncology, Hospital Universitario Río Hortega, Valladolid, Spain
• ¹¹ Medical Oncology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
• ¹² Medical Oncology, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain
• ¹³ Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada, Spain
• ¹⁴ Medical Oncology, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
• ¹⁵ Medical Oncology, Complejo Hospitalario Universitario Insular-Materno infantil de Gran Canaria, Las Palmas de Gran Canaria, Spain
• ¹⁶ Medical Oncology, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain
• ¹⁷ Universidad Autónoma de Madrid, School of Medicine - Hospital Universitario La Paz - CIBERONC, Madrid, Spain
• ¹⁸ Medical Oncology, Hospital Universitario Vall d’Hebron & Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
• ¹⁹ Medical Oncology, Hospital Universitario Lucus Augusti de Lugo, Lugo, Spain
• ²⁰ Medical Oncology, Complejo Asistencial de Segovia, Segovia, Spain
• ²¹ Medical Oncology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Ciudad de Murcia, Spain

Purpose: Combined BRAF/MEK inhibition with encorafenib (E) plus binimetinib (B) has demonstrated efficacy and tolerability in phase III clinical trials, and is the standard of care for advanced/metastatic BRAFV600-mutant melanoma. However, real-life evidence is limited, particularly in patients pre-treated with immune checkpoint inhibitors (ICI). Patients and methods: BECARE GEM 2002 was a retrospective, non-interventional study aimed at investigating the real-world effectiveness and tolerability of EB in patients with unresectable or metastatic BRAFV600-mutant melanoma conducted at 21 sites in Spain. The primary objective of this study was to characterise the population of patients receiving EB and assess the efficacy and tolerability of EB in real life. The study included patients treated according to standard clinical practice with EB as the 1st line or 2nd line after progression to ICI for an unresectable or metastatic stage. Patients who previously received treatment with BRAF and/or MEK inhibitor, other than as adjuvants, that ended ≥ 6 m before EB were not eligibleResults: From September 2021 to March 2023, 117 patients were included; 89 (76.1%) and 28 (23.9%) patients received EB as 1st line and 2nd line, respectively. The median follow-up was 13.8 months (95% CI: 12.0-17.4). In patients with EB as 1st line treatment, ORR and median PFS were 75% and 12 months (95% CI: 9.4-18.6), respectively. In patients with EB as 2nd line treatment after ICI, ORR and median PFS were 77.8% and 12.5 months (95% CI: 6.6-NA), respectively. In patients with brain metastasis ORR and median PFS were 70.8% and 6.3 months (95% CI: 7.0-6.4). Treatment-related adverse events of grade ≥3 were reported in 17 (14.5%) patients; transaminitis (9.4%) and diarrhoea (2.6%) were the most frequent adverse events.Conclusion: In this real-world study, EB treatment demonstrated effectiveness and a consistent safety profile in patients with BRAFV600-mutant melanoma treated according to standard clinical practice, including in those with prior ICI treatment and of brain metastasis; therefore, EB is a feasible treatment option for unresectable and metastatic melanoma.