BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC

Abstract

BRAF; Immunotherapy; NSCLC

BRAF; Immunoteràpia; NSCLC

BRAF; Inmunoterapia; NSCLC

Background Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. 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.

This study was funded by Bristol-Myers Squibb. The study was also supported by the European Union Horizon 2020 Research and Innovation program (European Commission) under grant agreement no. 875160. In addition, the project received funds from Instituto de Salud Carlos III (ISCIII) PI19/01652, PI21/01500 (Co-funded by European Regional Development Fund/ European Social Fund ‘A way to make Europe’/‘Investing in your future’ from European Commission) and grant RTC2019-007359–1 (BLI- O) from the Ministry of Science and Innovation. A.C-B. is supported by Sara Borrell fellowship grant n°CD19/00170. Instituto de Salud Carlos III (ISCIII). L R dL is supported by grant JDC2022-049091-I The Spanish State Research Agency.