BRAF L597

The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

Furthermore, TP53, LRP1B, STK11, SPTA1and MAGI2 were significantly over-mutated in Class II and III (p<0.06) and SETD2 is over-mutated in Class I (p<0.001), might suggesting relatively poor prognosis in NSCLC patients. Conclusions The characteristics of Chinese NSCLC were further explored, including BRAF mutation types, the incidence of related co-mutations and TMB value, which is helpful to formulate targeted therapy strategies to adapt to different types of BRAF mutation functions according to their genomic and clinical characteristics.

Introduction: Treatment with neoadjuvant nivolumab plus chemotherapy has demonstrated high efficacy in patients with locally advanced non-small-cell lung cancer (NSCLC)... Our data suggest that BRAF pathogenic variants may be a good prognostic factor in locally advance NSCLC patients treated with neoadjuvant chemo-immunotherapy.

MET fusions are a rare, but potentially actionable, genomic alteration. Our study provides a comprehensive characterization of MET fusions in NSCLC, revealing their diverse fusion partners and co-occurring genomic alterations. Further research is warranted to elucidate the clinical implications of MET fusions in the treatment of various types of cancer, including lung cancer.

The study highlights the heterogeneity of patients with BRAF class II and class III regarding histology and co-mutational status, with both classes equally frequent. A more granular investigation of non-V600X alterations and their associated clinical outcomes under different treatment approaches is ongoing.

P1/2, N=37, Terminated, Haihe Biopharma Co., Ltd. | N=150 --> 37 | Trial completion date: Dec 2024 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Mar 2023; Sponsor business decision

Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.

P1/2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Feb 2023 --> Feb 2024

Novel BRAF mutations and V600E were frequently detected in thyroid cancer of Libyan patients; this suggests a potential role of these novel mutations in carcinogenesis and in anti-EGFR therapy resistance.

P1/2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=38 --> 17

Rare BRAF mutations are not anecdotal in the metastatic melanoma population. Although data interpretation must remain careful owing to the limited size of some subsets of patients, non-E/K V600 BRAF mutations seem to confer a high sensitivity to targeted therapy, whereas MAPKis seem less effective in patients with non-V600 BRAF mutations. However, this strategy may be used as an alternative option in the case of immunotherapy failure in the latter population.

Four patients received combined BRAF/MEK inhibitors, two patients BRAF inhibitor monotherapy, and six patients were treated with ICI for advanced melanoma; four patients received adjuvant treatment with nivolumab. Given the few cases and the absence of randomized clinical trials, it is important to report clinical experiences, which can guide physicians in the treatment of melanomas harboring rare BRAF mutations.