BRAF D594G

BRAF class 3 mutations in NSCLC may identify a novel targetable population sensitive to EGFR-TKIs.

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.

The findings of this cohort study suggest that there are broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Identifying and classifying BRAF variants may be able to help guide precise treatment for patients with ICC.

We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

aBRAF mutations have historically been considered a favorable prognostic marker in mCRC. Co-mutation with RAS is frequent for both classes and portends poor survival in our real-world cohort. Furthermore, early onset aBRAF mCRC is associated with more aggressive disease.

This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.

Conclusion Our results - on a small number of patients - suggest that patients with rare BRAF mutations may have inferior survival outcomes with first line targeted treatment, compared with patients with classical BRAF mutations. Impact statement Our findings add to the limited clinical knowledge on rare BRAF mutations in melanoma and may help guide treatment decisions on this small subset of patients.

Vemurafenib and dabrafenib have already been approved for the treatment of melanoma, NSCLC and colorectal carcinoma. BRAF gene mutations, especially BRAF non-V600, was extensively mutated in Chinese multiple cancer types. Our revealed the potential targeted therapeutic strategies among non-V600 population with solid tumors should be considered in further study.

Preliminary data confirmed the safety of B+E and demonstrated evidence of anti-tumor activity in advanced cancer pts with non-V600E BRAF mts. Enrolment in the BEAVER trial is ongoing.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.