BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC.
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Provencio Mariano, Robado de Lope Lucía, Serna-Blasco Roberto, Nadal Ernest, Diz Tain Pilar, Massuti Bartomeu, González-Larriba José Luis, Insa Amelia, Sánchez-Hernández Alfredo, Casal-Rubio Joaquín, García-Campelo Rosario, Sequero López Silvia, Rogado Jacobo, Martínez-Martí Alex, Bosch-Barrera Joaquim, Bernabé Reyes, Vázquez Estévez Sergio, Ponce Santiago, de Castro Javier, Coves Sarto Juan, Reguart Noemí, Dómine Manuel, Aguilar Andrés, Majem Margarita, Estival Anna, Peña Cabia Silvia, López Martín Ana, Sala González María Ángeles, Cobo Manuel, Camps Carlos, Barneto Isidoro, Calvo Virginia, Collazo-Lorduy Ana, Cruz-Bermúdez Alberto, Romero Atocha
Аннотация
MATERIALS AND METHODS: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing.
RESULTS: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001).
CONCLUSION: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.