Tafinlar (dabrafenib) / Novartis, BeOne Medicines - LARVOL DELTA

Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment. (PubMed, Oncotarget) - "We present a 62-year-old male with mCRC harboring BRAF, MET, APC, TP53 and NRAS alterations, following FOLFOX and FOLFIRI, dabrafenib plus panitumumab, and a BRAF inhibitor clinical trial, each leading to initial responses followed by disease progression...Personalized combinations suggested included amivantamab-vmjw (anti-MET/EGFR antibody) (one-third standard dose) (for MET amplification and due to prior response to anti-EGFR antibody), trametinib, 1 mg po daily (MEK inhibitor for BRAF V600E mutation), and regorafenib (may have WNT inhibitor activity relevant to APC mutation; VEGFR activity relevant since TP53 alterations upregulate VEGF/VEGFR axis) starting at 40 mg po daily three weeks on, one week off. Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily. FOLFOXFIRI combined with bevacizumab, or liver-directed therapies for hepatic metastases, or..."

Biomarker • Journal • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • APC • NRAS • TP53

Molecular profiling in targeted therapy of gliomas in a community setting. (ASCO 2025) - "Accordingly, 11 patients received targeted therapy: 3 patients olaparib (RAD51C, BRCA2, H3.3 G34), 2 pembrolizumab (TMB high), 1 ivosidenib (IDH1), 1 selumetinib (NF1), 1 alpelisib (PIK3CA), 1 erdafitinib (FGFR3), 1 trametinib (NF1) and 1 dabrafenib/trametinib (BRAF) and then everolimus (TSC2). Molecular profiling nowadays is not only mandatory in glioma classification but can also provide additional therapies in patients with limited options."

IO biomarker • Tumor mutational burden • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • ATRX • BRAF • BRCA2 • EGFR • FGFR3 • IDH1 • MSI • NF1 • PD-L1 • PIK3CA • PTEN • RAD51C • TERT • TMB • TP53 • TSC2

Real-world Study of Darafenib or Trametinib and Clofarabine for High-risk/Recurrent/Refractory Langerhans Cell Histiocytosis in Children (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: West China Second University Hospital

New P2 trial • Real-world evidence • Langerhans Cell Histiocytosis • Pediatrics

Redifferentiation of Radioiodine-Refractory Thyroid Cancer following Genotype-Guided MAPK/BRAF Inhibition (SNMMI 2025) - P2 | "We here describe the final analysis of the primary endpoint (redifferentiation rate) of the ERRITI trial which evaluated efficacy and safety of a genotype-guided MAPK-modulation redifferentiation approach using trametinib (MEK inhibitor) in BRAF-WT and a trametinib/dabrafenib (BRAF inhibitor) combination in BRAF-MUT patients. We evaluated a total of 36 patients, of which 29 were included in the ERRITI trial and 7 underwent clinical redifferentiation therapy. In total, redifferentiation was successful in n=16/36 (44.4%) of patients and redifferentiation rate was not different between BRAF-MUT (n=7/15, 46.7%) and BRAF-WT (n=9/21, 42.9%) patients (X2 p=1). Redifferentiation rates of patients in the ERRITI trial were n=11/29 (37.9%) in total, n=4/11 (36.4%) in BRAF-MUT and n=7/18 (38.9%) in BRAF-WT patients."

Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Cardiovascular Safety Profile of BRAF and MEK Inhibitors in Melanoma: FAERS Data Through a Retrospective Disproportionality Analysis (2014-2023). (PubMed, Cancers (Basel)) - " Descriptive and disproportionality analyses were conducted on reports listing dabrafenib (D), vemurafenib (V), encorafenib (E), trametinib (T), cobimetinib (C), or binimetinib (B) as suspects in monotherapy or combination therapy (D + T, V + C, E + B), with melanoma as the indication and at least one cAE. Among embolic and thrombotic events, clinically significant SDRs were observed for disseminated intravascular coagulation with D + T (38; 10.22, 7.42-14.06) and pulmonary embolism with V + C (22; 2.79, 1.83-4.24). Our findings underscore the need for comprehensive CV monitoring in patients receiving BRAF/MEKi therapy to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations."

Journal • Retrospective data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Melanoma • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

Study of Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer (clinicaltrials.gov) - P3 | N=153 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2026 ➔ May 2027

Trial completion date • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Prevalence of histology-agnostic biomarkers in pure squamous cell carcinomas of the genitourinary tract. (ASCO 2025) - "There are 8 FDA-approved histology-agnostic treatments based on biomarker profiling: dostarlimab (dMMR/MSI-H), pembrolizumab (dMMR/MSI-H; TMB-H), larotrectinib (NTRK fusion), entrectinib (NTRK fusion), selpercatinib (RET fusion), trastuzumab deruxtecan (HER2 positive), and dabrafenib plus trametinib (BRAF V600E mutation). This study provides a comprehensive analysis of the genetic landscape of pure SCC of the GU tract that may inform future therapeutic strategies for this rare tumor with limited treatment options. Almost one-third of patients were TMB-High, reflecting a population that may benefit from immune checkpoint inhibitors monotherapy or combination strategies. Other histology-agnostic targets for current therapies were relatively infrequent."

Biomarker • IO biomarker • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Microsatellite Instability • Oncology • Squamous Cell Carcinoma • Urothelial Cancer • BAP1 • BRAF • BRCA1 • BRCA2 • BRIP1 • CDKN2A • CHEK2 • FAT1 • FGFR3 • HER-2 • KDM6A • MSI • NTRK • PALB2 • PIK3CA • PTEN • RAD51 • RET • TERT • TMB • TP53

Granulomatous interstitial nephritis in a patient with metastatic melanoma on target therapy with dabrafenib and trametinib: a case report (ERA 2025) - "Additional imaging revealed metastatic disease, and systemic treatment with nivolumab was initiated in addition to surgical removal...Despite these measures, the fever persisted, and he was admitted five days later to a local hospital, where he received broader antibiotic treatment with piperacillin/tazobactam, parenteral hydration, and a transfusion of two units of packed red cells for worsening anaemia... Acute kidney injury in patients receiving targeted therapy poses several management dilemmas. In most instances, kidney function will improve with conservative treatment. In a rare case of tubulointerstitial nephritis, prompt treatment with steroids improves kidney recovery, underscoring the importance of carefully considering the timing of kidney biopsy."

Case report • Clinical • Metastases • Acute Kidney Injury • Anemia • Cutaneous Melanoma • Dyslipidemia • Hematological Disorders • Infectious Disease • Melanoma • Nephrology • Oncology • Solid Tumor

Final results from DREAMseq in BRAFV600-mutant metastatic melanoma (YouTube) - "Michael Atkins, MD...discusses updated outcomes from the DREAMseq trial (NCT02224781), which compared initial treatment with nivolumab and ipilimumab versus dabrafenib and trametinib in patients with treatment-naïve BRAFV600-mutant metastatic melanoma."

Interview • Video

Metastatic pancreatic cancer with activating BRAF V600E mutations: A case report. (PubMed, World J Clin Cases) - "BRAF alterations are infrequent in PC. This case highlights the significance of molecular profiling in patients with PC, especially in patients with a high tumor burden."

IO biomarker • Journal • Anorexia • Oncology • Pain • Pancreatic Cancer • Solid Tumor • BRAF • CA 19-9 • CEACAM5

Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study (clinicaltrials.gov) - P4 | N=335 | Not yet recruiting | Sponsor: Fujian Medical University

IO biomarker • New P4 trial • Real-world evidence • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Primary rectal malignant melanoma with schistosomiasis. (PubMed, Intractable Rare Dis Res) - "The patient subsequently received Dabrafenib and Trametinib therapy and remained disease-free for 5 years postoperatively, with no evidence of recurrence. This case highlights the potential treatment strategies for this rare carcinoma and underscores the need for further investigation into the relationship between schistosomiasis and melanoma."

Journal • Colorectal Cancer • Infectious Disease • Melanoma • Oncology • Rectal Cancer • Solid Tumor

Feasibility of Short-Term Redifferentiation in Patients with Radioactive Iodine-Refractory Metastatic Thyroid Cancer. (PubMed, J Nucl Med) - "Recent studies have used tyrosine kinase inhibitors (TKIs) for 3-6 wk to achieve redifferentiation, but preclinical data suggest that maximal effects occur within 8-12 d. In this retrospective study, 8 patients with metastatic radioactive iodine-refractory TC received trametinib plus dabrafenib (for BRAF-mutated disease) or trametinib alone (for BRAF wild-type disease) for 10 d. Iodine uptake was assessed by 123I-scintigraphy; responders received high-dose radioactive iodine therapy, and nonresponders continued TKIs for another 10 d. Two patients (both with BRAF wild-type disease) achieved successful iodine uptake restoration with significant thyroglobulin reduction after radioactive iodine therapy. Longer treatment did not provide any additional benefit. Larger prospective trials are needed to confirm these findings."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

Extended Survival in Stage IV Papillary Thyroid Carcinoma presenting with Anaplastic Transformation (ENDO 2025) - "She briefly received chemotherapy with paclitaxel and carboplatin in November 2018 with RAI and anti-BRAF regimen of dabrafenib and trametinib from January to April 2019 which was discontinued for intolerance...The patient continues with follow-up almost 6 years from diagnosis on thyroid hormone suppression with levothyroxine. This case demonstrates an atypical course of anaplastic thyroid cancer... This case demonstrates an atypical course of anaplastic thyroid cancer. The patient had good response to surgery and chemoradiation and continues to fare well on thyroid hormone suppression almost 6 years from diagnosis, a very rare prognosis.Of note, the sigmoid colon uptake positive on initial PET CT disappeared on repeat imaging studies. It is unclear if the sigmoid colon uptake had been a false positive result or had resolved with treatment."

Metastases • Endocrine Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Spontaneous Intracranial Hypotension in a Patient with Papillary Thyroid Carcinoma Treated with Dabrafenib and Trametinib: A Case Report (ENDO 2025) - "This case highlights the importance of recognizing intracranial hypotension as a rare but significant side effect of BRAF/MEK inhibition therapy. Early recognition and intervention, including imaging and possible therapy discontinuation, can lead to symptom resolution and prevent long-term complications. Further investigation is warranted to establish the mechanism underlying this association and to optimize management strategies for affected patients."

Case report • Clinical • Cardiovascular • CNS Disorders • Endocrine Cancer • Hypertension • Hypotension • Immunology • Oncology • Pain • Solid Tumor • Systemic Inflammatory Response Syndrome • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

Transdifferentiation of Classic Papillary Thyroid Carcinoma to a High Grade Mucoepidermoid Carcinoma: A Case Report With Molecular Insights. (ENDO 2025) - "Total thyroidectomy was performed 11 years ago followed by 150 mCi 131I RAI therapy under levothyroxine withdrawal with a post-therapy scan revealing thyroid bed uptake...Dabrafenib and trametinib therapy initially resulted in partial response but soon afterwards, the disease rapidly progressed, and the patient unfortunately succumbed to the disease. We describe the potential molecular mechanisms of EMT that may have transformed a cPTC to a high-grade MEC due to PVs in genes involved in chromatin remodeling (ARID2) and signal transduction (NOTCH2 and PIK3CB). This may have led to aberrant histopathological differentiation, as in this patient, who clinically manifested RAI-refractoriness and rapidly progressive disease."

Case report • Clinical • Endocrine Cancer • Oncology • Pancreatic Cancer • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • ARID2 • BRAF • NKX2-1 • NOTCH2 • PAX8 • PIK3CB • TP53

Structural Insights into allosteric inhibition of HRI kinase by heme binding via HDX-MS. (PubMed, Biochem J) - "We examined several competitive ATP-mimetic inhibitors-Dabrafenib, Encorafenib, and GCN2iB-and compared them to the heme-mimetic allosteric inhibitor, hemin. Our analysis revealed that hemin inhibition induces large-scale structural rearrangements in HRI, which are not observed with ATP-mimetic inhibitors. Our results suggest that HRI may be inhibited using two distinctly different modalities which may guide future drug development."

Journal • CNS Disorders • Oncology

A Case of Anaplastic Thyroid Carcinoma That Presented as Metastatic Disease of Unknown Primary (ENDO 2025) - "ATC can be a significant diagnostic challenge and often requires thorough pathologic evaluation with targeted immunohistochemistry. Early identification of targetable somatic mutations can significantly aid selection of effective therapy. In this case, a therapy of dabrafenib and trametinib achieved a highly favorable outcome for BRAF-positive ATC."

Clinical • Metastases • Endocrine Cancer • Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • PAX8

Favorable Response of a rare BRAF G469A-Mutated Medullary Thyroid Carcinoma to Dabrafenib and Trametinib Combination Therapy (ENDO 2025) - "This case highlights a very rare BRAF G469A mutation in a patient with MTC. The observed response to dabrafenib/trametinib, similar to responses seen in reports of non-small cell lung cancer with the same mutation, suggests a potential therapeutic role for this combination in this specific molecular subtype of MTC. Further investigation is needed to determine the durability of response and underlying mechanisms of action."

Combination therapy • Endocrine Cancer • Endocrine Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • BRAF • RET

Induction therapy with dabrafenib, trametinib, and PD-1 inhibitor and surgical conversion in unresectable stage III non-small cell lung cancers with BRAF V600E mutation: 2 cases. (PubMed, Lung Cancer) - "These cases suggest that targeted-immunotherapy combinations may present a promising treatment option for tumor downstaging and surgical conversion in unresectable stage III NSCLC with BRAF V600E mutation. However, prospective studies with larger cohorts and longer follow-up are warranted to validate this strategy."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Anxiety, depression, fear of cancer recurrence (FCR) and health-related quality of life (HRQL) in people with melanoma receiving adjuvant therapies. (ASCO 2025) - "Funded by No funding sources reported Background: One year of adjuvant anti-programmed cell death protein-1 (anti-PD1) or dabrafenib-trametinib are standards of care for patients (pts) with resected stage III-IV melanoma. A significant number of pts report anxiety, depression, and clinically significant FCR up to 2 years post initiation of adjuvant therapy, which is associated with worse HRQL. Screening for psychological issues can identify those who may benefit from psychological and/or pharmacological intervention to improve disease outcomes."

Clinical • HEOR • CNS Disorders • Depression • Melanoma • Mood Disorders • Oncology • Psychiatry • Solid Tumor

Financial toxicity and employment outcomes in people with melanoma receiving adjuvant therapies. (ASCO 2025) - "Funded by No funding sources reported Background: One year of adjuvant anti-programmed cell death protein-1 (anti-PD1) or dabrafenib-trametinib are standards of care for patients (pts) with resected stage III-IV melanoma. Half of pts reported reduced working hours and income 12 months post therapy initiation, mostly due to ongoing symptoms. A third reported financial toxicity at 12 months, even with universal healthcare. This data can inform shared decision-making about risks and benefits of adjuvant therapy and highlights the importance of screening for financial toxicity to identify pts who require support."

Clinical • Melanoma • Oncology • Solid Tumor

IMMUNORARE5: A national platform of 5 academic phase II trials coordinated by Lyon University Hospital to assess the safety and the efficacy of the immunotherapy with domvanalimab + zimberelimab combination in patients with advanced rare cancers—The Anaplastic Thyroid Carcinomas Cohort. (ASCO 2025) - P2 | "In such patients carrying the BRAFV600 mutation (20-30%), the standard 1st-line treatment relies on dabrafenib & trametinib...In DUTHY trial (Durvalumab + tremelimumab), the 6month-OS was 65.6% in ATC...Translational research projects will be developed aiming at deciphering cellular and molecular mechanisms involved in response to treatment. Moreover, data from the prospective database of the ENDOCAN-TUTHYREF network will be investigated to build a synthetic historical arm representative of the efficacy of the standard treatments in a similar population of patients."

Clinical • IO biomarker • Metastases • P2 data • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • TIGIT

Outcomes of patients treated with dabrafenib and trametinib who developed pyrexia syndrome and severe/complicated pyrexia syndrome. (ASCO 2025) - "Pyrexia syndrome is the most common adverse event in patients treated with dabrafenib and trametinib. While patients who develop pyrexia and severe/complicated pyrexia are more likely to require their medication to be discontinued, they also remain on treatment for longer periods, suggesting that pyrexia may be a positive prognostic marker of treatment efficacy. This speaks to the importance of developing strategies for the management of pyrexia syndrome."

Clinical • Brain Cancer • Endocrine Cancer • Glioma • Hypotension • Infectious Disease • Lung Cancer • Melanoma • Nephrology • Oncology • Renal Disease • Solid Tumor • Thyroid Gland Carcinoma • Wilms Tumor • BRAF

Tumor-agnostic therapies in a high-volume Brazilian center: Real-world challenges and opportunities. (ASCO 2025) - "Forty pts (24%) received TAT: 37% checkpoint inhibitors, 12.5% Trastuzumab deruxtecan, 7.5% trastuzumab plus pertuzumab, crizotinib and sotorasib, 5% dabrafenib plus trametinib and 23% others. In this real-world retrospective analysis of a high-volume Latin American center, CGP enabled the identification of agnostic biomarkers, offering targeted therapeutic options and improved outcomes for select individuals. The analysis was limited by unmatched distribution of tumor types, lacking treatment history and comorbidities among groups. Limited access to TAT may reflect the timing of tests, pre-dating some agnostic approvals, as well as the high cost and restricted availability of these therapies."

Clinical • Pan tumor • Real-world • Real-world evidence • Tumor mutational burden • Lung Cancer • Microsatellite Instability • Oncology • Solid Tumor • ALK • BRAF • FGFR • HER-2 • KRAS • MSI • NRG1 • NTRK • TMB