Dabrafenib–trametinib combination therapy re-challenge in advanced BRAFV600E-mutant non–small-cell lung cancer

Kashizaki, Fumihiro; Tanaka, Arihito; Hattori, Shigeaki; Sugimoto, Shunsuke

doi:10.1016/j.ejca.2020.11.002

Cited by 7 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the tumor progressed after the first-line MET inhibitor treatment but responded to capmatinib. The reason is also unclear but may be attributed to the anticancer drugs administered between the three MET inhibitors ( 11 ), as well as slight differences in the mechanism of action among these MET inhibitors ( 12 ). While these factors partially explain this fact, the lack of concrete evidence to explain the specific phenomenon is noticeable.…”

Section: Discussionmentioning

confidence: 99%

Effective treatment of MET exon 14 skipping mutation-positive non-small cell lung cancer using capmatinib following serious maculopapular rash caused by two MET inhibitors: a case report

Kashizaki,

Okazaki,

Tsuchiya

et al. 2024

AME Case Rep

View full text Add to dashboard Cite

Background Multi-gene panel testing and advancements in molecular targeted therapy have improved the overall survival of patients with driver mutation-positive non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor ( MET ) exon 14 skipping mutation-positive NSCLC, which remains untreated with MET inhibitors, shows a poorer prognosis than do cases of NSCLC without MET mutations. However, serious treatment-related adverse events (TRAEs) act as substantial treatment barriers. Case Description Herein, we report a case of advanced NSCLC in a male in his 40s with MET exon 14 skipping mutation. A MET-inhibitory investigational drug was administered as first-line treatment; the development of grade 3 maculopapular rash necessitated dose reduction, which resulted in disease progression. Tepotinib was then administered with dexamethasone as a third-line treatment but was discontinued owing to the re-development of the grade 3 maculopapular rash. Finally, capmatinib administration as the fifth-line treatment appeared partially effective, with no serious adverse events. The patient could successfully resume work. Conclusions This is the first report of MET exon 14 skipping mutation-positive NSCLC wherein partial response was achieved without severe TRAEs by alternating between two MET inhibitors. If no alternative treatments are available, cautious repeated re-administration of MET inhibitors after resolving serious rashes can be considered a potential approach.

show abstract

Section: Discussionmentioning

confidence: 99%

Effective treatment of MET exon 14 skipping mutation-positive non-small cell lung cancer using capmatinib following serious maculopapular rash caused by two MET inhibitors: a case report

Kashizaki,

Okazaki,

Tsuchiya

et al. 2024

AME Case Rep

View full text Add to dashboard Cite

show abstract

“…A similar approach has been proposed in a recent case of successful re-challenge therapy with combined BRAF and MEK inhibition following a series of subsequent chemotherapy treatments. The response mechanism may involve the establishment of a "drug-free" environment, leading to a decrease in the number of heterogeneous tumor cells previously exposed to BRAF and MEK inhibitors, ultimately resulting in a successful re-challenge for certain patients [143]. Downstream inhibition of the terminal pathway kinase, ERK, represents a promising approach to suppress any upstream pathway activation or reactivation.…”

Section: Discussionmentioning

confidence: 99%

RAF and MEK Inhibitors in Non-Small Cell Lung Cancer

Adamopoulos,

Papavassiliou,

Poulikakos

et al. 2024

IJMS

View full text Add to dashboard Cite

Lung cancer, despite recent advancements in survival rates, represents a significant global health burden. Non-small cell lung cancer (NSCLC), the most prevalent type, is driven largely by activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) and receptor tyrosine kinases (RTKs), and less in v-RAF murine sarcoma viral oncogene homolog B (BRAF) and mitogen-activated protein-kinase kinase (MEK), all key components of the RTK-RAS-mitogen-activated protein kinase (MAPK) pathway. Learning from melanoma, the identification of BRAFV600E substitution in NSCLC provided the rationale for the investigation of RAF and MEK inhibition as a therapeutic strategy. The regulatory approval of two RAF-MEK inhibitor combinations, dabrafenib–trametinib, in 2017, and encorafenib–binimetinib, in 2023, signifies a breakthrough for the management of BRAFV600E-mutant NSCLC patients. However, the almost universal emergence of acquired resistance limits their clinical benefit. New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.

show abstract

“…In another study, a patient with NSCLC with advanced BRAF V600E mutation was resistant to BRAF-targeted therapy in first-line therapy and therefore received chemotherapy as second-line therapy. After progression to chemotherapy, BRAF-targeted therapy was re-challenged, and the patient benefited ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics, Co-Mutations, and Treatment Outcomes in Advanced Non-Small-Cell Lung Cancer Patients With the BRAF-V600E Mutation

Shen

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundLimited treatment outcome data is available for advanced non-small cell lung cancer (NSCLC) patients with BRAF V600E mutations. In this multicenter study, we describe therapeutic options and survival outcomes for patients with mutated BRAF V600E.MethodThis was a retrospective study in which BRAF V600E-mutated advanced NSCLC patients were retrospectively recruited between January 2015 and December 2021 and had their clinical characteristics, co-mutations, and treatment efficacy assessed.ResultsFifty-three patients with BRAF V600E-mutant advanced NSCLC were included in the study, of which 64.2% were non-smokers, and the BRAF V600E mutation was more prevalent in men (52.8%). In addition, 96.2% of the patients had adenocarcinoma, and most (96.2%) received first-line therapy (23.5% anti-BRAF), with a progression-free survival (PFS) and overall survival (OS) of 10.0 [95% confidence interval (CI): 1.5–36.0 months] and 24.0 months [95% CI: 3.0–53.0 months], respectively. Twenty-three patients (43.4%) received second-line treatment (39.1% anti-BRAF), and PFS and OS were 5.0 [95% CI: 1.0–21.0 months] and 13.0 months [95% CI: 1.5–26.0 months], respectively. BRAF and MEK-targeted therapy (dabrafenib plus trametinib) produced longer PFS compared with that of chemotherapy with or without bevacizumab as a first-line (NA vs. 4.0 months, P = 0.025) or second-line therapy (6.0 vs. 4.6 months, P = 0.017). NSCLC patients harboring driver oncogene mutations such as BRAF V600E, EGFR, or ALK should be treated using targeted therapies. Concurrent TP53 mutations were the most common, affecting 11.3% (n = 6) of the patients, followed by EGFR 19 Del (n = 5). Patients with concurrent mutations had shorter PFS (9.0 vs. 10.0 months, P = 0.875) and OS (14.0 vs. 15.0 months, P = 0.555) than those without these mutations.ConclusionThese results suggest that combined BRAF- and MEK-targeted therapy is effective in BRAF V600E-mutated advanced NSCLC patients. Dabrafenib and trametinib re-challenge is also an option for patients with BRAF V600E-mutated NSCLC.

show abstract

Dabrafenib–trametinib combination therapy re-challenge in advanced BRAFV600E-mutant non–small-cell lung cancer

Cited by 7 publications

References 2 publications

Effective treatment of MET exon 14 skipping mutation-positive non-small cell lung cancer using capmatinib following serious maculopapular rash caused by two MET inhibitors: a case report

Effective treatment of MET exon 14 skipping mutation-positive non-small cell lung cancer using capmatinib following serious maculopapular rash caused by two MET inhibitors: a case report

RAF and MEK Inhibitors in Non-Small Cell Lung Cancer

Clinical Characteristics, Co-Mutations, and Treatment Outcomes in Advanced Non-Small-Cell Lung Cancer Patients With the BRAF-V600E Mutation

Contact Info

Product

Resources

About