Safety of combining dabrafenib plus trametinib in elderly BRAF V600 mutation-positive advanced melanoma patients: real-world data analysis of Spanish patients (ELDERLYMEL)
Por:
Gonzalez-Barrallo, I, Rubio, VEC, Medina, J, Espana, S, Mujika, K, Majem, M, Aguado, C, Suarez, MAC, Palacio, I, Osterloh, L, Martinez-Fernandez, A, Garcia-Castano, A
Publicada:
1 oct 2022
Resumen:
Efficacy and safety of dabrafenib and trametinib in metastatic melanoma have been demonstrated in two-phase III and one-phase I/II clinical trials. However, patients at least 75 years old (y.o.) were largely underrepresented. Additionally, the safety profile of dabrafenib and trametinib based on age is unknown. ELDERLYMEL is a retrospective noninterventional multicenter study, describing the effectiveness and safety of at least 75 y.o. patients compared with less than 75 y.o. patients with advanced BRAF V600-mutated melanoma treated with dabrafenib plus trametinib or dabrafenib monotherapy. A total of 159 patients were included, 130 less than 75 y.o. and 29 at least 75 y.o. Clinical features were similar between the groups, except in the number of comorbidities, number of metastatic sites, Eastern Cooperative Oncology Group (ECOG) performance status, and BRAF V600-mutation type. Five patients per group received dabrafenib monotherapy. There were no differences in adverse events (AEs) rate or grade between the groups. However, AE profiles were different between the groups, being pyrexia infrequent in patients at least 75 y.o. (13.8% vs. 42.3%; P = 0.005). Dabrafenib and trametinib dose intensities were lower in at least 75 y.o. patients (P = 0.018 and P = 0.020), but there were no differences in effectiveness between the groups. Finally, in a multivariate analysis, sex (female) was the only variable independently associated with an increased risk of AE grade >= 3. Data from the ELDERLYMEL study demonstrate that dabrafenib plus trametinib is safe and effective in at least 75 y.o. patients with advanced BRAF V600-mutated melanoma without increasing toxicity. Additionally, we describe a different safety profile depending on age and sex.
Filiaciones:
Gonzalez-Barrallo, I:
Hosp Clin Univ Valencia, Oncol Dept, Valencia, Spain
Rubio, VEC:
Hosp Univ Torrecardenas, Dept Med Oncol, Almeria, Spain
Medina, J:
Virgen de la Salud Hosp, Div Med Oncol, Toledo, Spain
Espana, S:
Germans Trias & Pujol Univ Hosp, Catalan Inst Oncol ICO, Med Oncol Serv, Barcelona, Spain
Germans Trias & Pujol Fdn IGTP, Hlth Sci Res Inst, Badalona, Spain
Mujika, K:
Hosp Univ Donostia Onkol, Med Oncol Dept, UGC Oncol Gipuzkoa, Gipuzkoa, Spain
Majem, M:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Aguado, C:
Hosp Univ Clin San Carlos, Med Oncol Dept, Madrid, Spain
Suarez, MAC:
Hosp Univ Nuestra Senora de Candelaria, Med Oncol Dept, Santa Cruz De Tenerife, Spain
Palacio, I:
Hosp Univ Cent Asturias, Med Oncol, Oviedo, Spain
Osterloh, L:
Novartis Farmaceut SA, Med Dept, Barcelona, Spain
Martinez-Fernandez, A:
Novartis Farmaceut SA, Med Dept, Barcelona, Spain
Garcia-Castano, A:
Hosp Univ Marques de Valdecilla, Dept Med Oncol, Ave Valdecilla 25, Santander 39008, Spain
|