Clinicogenomic Features and Targetable Mutations in NSCLCs Harboring BRAF Non-V600E Mutations: A Multi-Institutional Genomic Screening Study (LC-SCRUM-Asia)

Sakai, Tetsuya; Matsumoto, Shingo; Ueda, Yuki; Shibata, Yuji; Ikeda, Takaya; Nakamura, Atsushi; Kodani, Masahiro; Ohashi, Kadoaki; Furuya, Naoki; Izumi, Hiroki; Nosaki, Kaname; Umemura, Shigeki; Zenke, Yoshitaka; Udagawa, Hibiki; Sugiyama, Eri; Yoh, Kiyotaka; Goto, Kōichi

doi:10.1016/j.jtho.2023.07.024

Cited by 8 publications

(11 citation statements)

References 26 publications

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“…Common concurrent mutations included alterations in the TP53 and SETD2 genes and the PI3K (e.g., PIK3CA E545K, PTEN R14K) and MAPK (e.g., KRAS G12C) pathways 17 , 18 , 61 , 69 . The incidence of concurrent TP53 or RAS gene family mutations was higher with BRAF class II or III mutations than class I mutations 31 , 33 , 70 . In several studies, the presence of a concurrent mutation in TP53, PIK3CA, KRAS, or PTEN was associated with poorer outcomes 17 , 61 , 69 .…”

Section: Treatment Landscapementioning

confidence: 92%

“…While those retrospective studies also reported a shorter PFS in patients with V600E mutations (4.1–5.2 months) versus non-V600E mutations (6.4–8.9 months), another retrospective study reported that carboplatin-pemetrexed in patients with treatment-naive BRAF-mutant metastatic NSCLC resulted in longer PFS in patients with class I mutations (6.2 months) versus class II or III mutations (3.3 months and 4.9 months, respectively) 33 . Additionally, in a multi-institutional prospective lung cancer screening project, median PFS with platinum-containing chemotherapy was longer in patients with class I mutations (11.5 months) than in those with class III mutations (5.3 months) 31 . Several trials demonstrated that BRAF monotherapy or BRAF plus MEK inhibitor therapy was effective in patients who had progressed on chemotherapy 10 , 15 , 18 , 66 .…”

Section: Treatment Landscapementioning

confidence: 99%

“…Smoking history can be associated with BRAF mutations, as well as KRAS, MET , and other mutations 9 , 28 , 29 . However, a few studies have also suggested that BRAF V600E is less associated with smoking history than other BRAF mutations 26 , 30 , 31 . Therefore, all patients with advanced NSCLC regardless of smoking history should undergo broad-based mutation testing, including BRAF 5 , 21 , 22 .…”

Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

“…The prognostic implication of BRAF mutation status is inconclusive due to small patient numbers and conflicting studies 8 , 26 , 28 . However, a few studies reported worse outcomes with chemotherapy in patients with V600E mutations versus wild type (WT) BRAF and conflicting results for V600E versus non-V600E mutations 6 , 31 – 33 . In addition to the small patient number, discrepancies in patient characteristics and prognosis could be attributed to the heterogeneity of BRAF mutations in NSCLC 33 , 34 .…”

Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

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BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Planchard,

Sanborn,

Negrao

et al. 2024

npj Precis. Onc.

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In this review, we cover the current understanding of BRAF mutations and associated clinical characteristics in patients with metastatic NSCLC, approved and emerging treatment options, BRAF sequencing approaches, and unmet needs. The BRAFV600E mutation confers constitutive activity of the MAPK pathway, leading to enhanced growth, proliferation, and survival of tumor cells. Testing for BRAF mutations enables patients to be treated with therapies that directly target BRAFV600E and the MAPK pathway, but BRAF testing lags behind other oncogene testing in metastatic NSCLC. Additional therapies targeting BRAFV600E mutations provide options for patients with metastatic NSCLC. Emerging therapies and combinations under investigation could potentially overcome issues of resistance and target non-V600E mutations. Therefore, because targeted therapies with enhanced efficacy are on the horizon, being able to identify BRAF mutations in metastatic NSCLC may become even more important.

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Section: Treatment Landscapementioning

confidence: 92%

Section: Treatment Landscapementioning

confidence: 99%

Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

See 2 more Smart Citations

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Planchard,

Sanborn,

Negrao

et al. 2024

npj Precis. Onc.

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show abstract

“…8 Recent findings indicate that NSCLC patients with BRAF class III mutations have a poorer response to platinum-containing chemotherapies compared to those with BRAF V600E mutations. 9 The BRAF G466V mutation, is a class III alteration, potentially confers increased tumor aggressiveness 10 and lacks targeted therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

Clinical Response of Advanced Lung Adenocarcinoma with Class III BRAF G466V Missense Mutation to Dabrafenib and Trametinib: A Case Report

Fang,

Xu,

Gong

et al. 2024

OTT

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BRAF is a pivotal driver gene in cancer development. Based on this, the combination of dabrafenib and trametinib was approved for treating NSCLC patients with BRAF V600E mutations. However, the majority of BRAF mutations in lung cancer are non-V600E variants, particularly class III mutants, which currently lack targeted therapeutic options and result in unfavorable clinical outcomes. Case Presentation: We present a case of advanced lung adenocarcinoma with a class III BRAF G466V mutation. The patient experienced significant pleural and pericardial effusion, leading to chest tightness and an inability to lie flat. Severe pain and limited mobility from lumbar destruction seriously affected the patient's quality of life. Due to the patient's intolerance to chemotherapy, dabrafenib and trametinib combination therapy was chosen. After three months of targeted therapy, the patient's overall condition significantly improved, enabling self-care, and achieving partial response (PR) as an indicator of treatment efficacy. Conclusion:The combination therapy of dabrafenib and trametinib demonstrates remarkable clinical benefits for lung adenocarcinoma patients with the BRAF G466V mutation. Targeted therapy should be considered for patients with BRAF class III mutations, especially those in poor general condition and may not tolerate chemotherapy.

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Osimertinib‐induced BRAF mutation in a single metastatic lesion among multiple pulmonary lesions in a case of lung cancer with EGFR exon 19 deletion

Miura,

Goto

et al. 2024

Respirology Case Reports

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One of the resistant mechanisms of EGFR‐TKIs is BRAF V600E mutation. Herein, we present the case of a 54‐year‐old Japanese female who underwent a right middle lobectomy for pathological stage IIB lung adenocarcinoma. One year and nine months after the surgery, she developed multiple intrapulmonary metastases. Osimertinib was administered due to EGFR exon 19 deletion. Although all intrapulmonary metastases had shrunk, the nodule at the superior segment of left lung enlarged after postoperative 4 years. The tumour was resected and BRAF V600E mutation and exon 19 deletion were detected. Three months after treatment with dabrafenib and trametinib instead of osimertinib, the remaining intrapulmonary metastases increased again. The continued growth of the metastatic foci even after EGFR‐TKI may indicate an acquired resistance. Thus, a repeat biopsy will aid in confirming the new gene expression. It should have been necessary to administer an additional dose of dabrafenib and trametinib without discontinuing osimertinib.

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Clinicogenomic Features and Targetable Mutations in NSCLCs Harboring BRAF Non-V600E Mutations: A Multi-Institutional Genomic Screening Study (LC-SCRUM-Asia)

Cited by 8 publications

References 26 publications

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Clinical Response of Advanced Lung Adenocarcinoma with Class III BRAF G466V Missense Mutation to Dabrafenib and Trametinib: A Case Report

Osimertinib‐induced BRAF mutation in a single metastatic lesion among multiple pulmonary lesions in a case of lung cancer with EGFR exon 19 deletion

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