Outcomes After Treatment With Cobimetinib in Patients With Rosai-Dorfman Disease Based on <i>KRAS</i> and <i>MEK</i> Alteration Status

Abeykoon, Jithma P.; Rech, Karen L.; Young, Jason R.; Ravindran, Aishwarya; Ruan, Gordon; Dasari, Surendra; Morlote, Diana; King, Rebecca; Rummage, Claire; Zanwar, Saurabh; Acosta-Medina, Aldo M.; Tobin, W. Oliver; Shah, Mithun Vinod; Bennani, N. Nora; Vassallo, Robert; Ryu, Jay H.; Koster, Matthew J.; Davidge‐Pitts, Caroline; Witzig, Thomas E.; Goyal, Gaurav; Go, Ronald S.

doi:10.1001/jamaoncol.2022.4432

Cited by 27 publications

(12 citation statements)

References 15 publications

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“…KRAS and MEK gene alterations are present in approximately 40% of RDD cases. A recent retrospective cohort study demonstrated clinically significant response rates using the MEK inhibitor cobimetinib in KRAS and MEK -variant RDD ( 26 ). BRAF oncogene mutations are a well-established molecular driver and treatment target in other histiocytoses such as Langerhans cell histiocytosis and Erdheim-Chester disease ( 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

et al. 2022

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BRAF V600E oncogene mutations have been reported in multiple central nervous system (CNS) tumor types, and emerging evidence supports the use of targeted therapy in BRAF-mutated gliomas. BRAF oncogene mutations have been recently identified in Rosai-Dorfman disease (RDD)—a rare non-Langerhans cell histiocytosis. This series describes three patients from two neurosurgical centers in Ireland with BRAF V600E-mutated CNS tumors. The study participants include a 19-year-old male patient with ganglioglioma with anaplastic features, a 21-year-old male patient with CNS involvement of RDD, and a 28-year-old female patient with ganglioglioma with anaplastic features. Two patients received radiation with concurrent temozolomide before BRAF-targeted therapy. This case series describes clinical and radiological responses to BRAF-targeted therapy in BRAF V600E-mutated gliomas across multiple tumor grades and is only the second published report of response to targeted therapy in BRAF-mutated RDD. The durability of disease control with BRAF-targeted therapy was generally superior to that achieved with chemoradiation; one patient has experienced ongoing disease control for 5 years. The reported case of treatment response in BRAF-mutated RDD supports the strategy of genotyping and utilization of targeted therapy in this rare disease. The optimal sequencing of BRAF-targeted therapy in BRAF-mutated gliomas/glioneuronal tumors remains unclear, and further prospective studies are required to guide the use of genome-matched therapy in this patient population.

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Section: Discussionmentioning

confidence: 99%

Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

et al. 2022

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“…The ALK inhibitor, crizotinib, achieved 90% and 86% ORR and 80% and 36% complete response in anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastoma (IMT), respectively. 69 Subsequently, ALK inhibitors were shown to be effective in malignant peritoneal mesothelioma, neuroblastoma, renal cell carcinoma, colorectal cancer, and melanoma. 70 – 72 The high remission rate of ALK inhibitors for ALK-driven NSCLC, ALCL, and IMT unlocked the “single-target to single-drug” model in the epoch dominated by chemotherapy, which was the most typical pattern of basket trials.…”

Section: Discovery: Clinical Dilemma Prompting An Exploration Of New ...mentioning

confidence: 99%

New clinical trial design in precision medicine: discovery, development and direction

Duan,

Qin,

Jiao

et al. 2024

Sig Transduct Target Ther

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In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the “Precision Pro”, “Dynamic Precision”, and “Intelligent Precision”. This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.

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“…Diamond et al 23 demonstrated an overall response rate (per investigators' defined positron emission tomography [PET] response criteria in solid tumors) of 89% in a cohort of 18 patients, which resulted in FDA approval. In addition, a retrospective study of cobimetinib in RDD demonstrated an overall response rate of 63% 24 .…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of non-Langerhans cell histiocytosis with the MEK inhibitor trametinib: a multicenter analysis

et al. 2023

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Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs) for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at four major US care centers. The most common treatment-related toxicity was rash (27% of patients). For most patients, disease was effectively managed at lower doses (0.5-1.0 mg trametinib daily). The response rate in the 17 evaluable patients was 71% (with 73% (8/11) without a detectable BRAF V600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, while median progression-free and overall survival had not been reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations); or alterations in other genes involved in the MAPK pathway, e.g., MAP2K1, NF1, GNAS or RAS. Most patients required lower than standard doses of trametinib but were responsive to the lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.

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Outcomes After Treatment With Cobimetinib in Patients With Rosai-Dorfman Disease Based on KRAS and MEK Alteration Status

Cited by 27 publications

References 15 publications

Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

Case report: BRAF-inhibitor therapy in BRAF-mutated primary CNS tumours including one case of BRAF-mutated Rosai-Dorfman disease

New clinical trial design in precision medicine: discovery, development and direction

Successful treatment of non-Langerhans cell histiocytosis with the MEK inhibitor trametinib: a multicenter analysis

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