Mekinist (trametinib) / Japan Tobacco, Novartis, BeOne Medicines - LARVOL DELTA

Redifferentiation of BRAF V600E-Mutant Radioiodine-Refractory Papillary Thyroid Carcinoma with Dabrafenib and Trametinib, Enabling a Third Radioiodine Therapy: A Case Report (EANM 2026) - "Sorafenib was initiated in January 2023 and later switched to combined dabrafenib and trametinib in May 2025 due to disease progression. BRAF/MEK inhibition can restore radioiodine uptake in a subset of lesions in BRAF V600E-mutant RAIR differentiated thyroid carcinoma, enabling reintroduction of [¹³¹I]NaI therapy. However, the coexistence of radioiodine-avid and non-avid lesions highlights the biological heterogeneity of the disease and supports a combined treatment approach. Functional imaging with [¹³¹I] NaI SPECT/CT may help identify redifferentiation and guide individualized, multimodal management."

Case report • Clinical • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF • TG

Prognostic Value of Baseline Thyroglobulin with Complementary FDG PET Stratification in BRAF V600E-Mutant Radioiodine-Refractory Papillary Thyroid Carcinoma Treated with Dabrafenib plus Trametinib (EANM 2026) - "Dabrafenib plus trametinib demonstrates promising efficacy and a favorable safety profile in BRAF V600E-mutant RAI-R PTC. Our findings highlight that baseline Tg is a robust prognostic marker. Furthermore, integration with FDG PET-derived SUVmax may enhance risk stratification, potentially guiding personalized therapeutic strategies in the era of targeted therapy."

FDG PET • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF

Adjuvant anti-TIGIT plus anti-PD-1 in melanoma: A necessary failure that clarifies the path forward. (PubMed, Transl Oncol) - "The phase 3 KEYVIBE-010 trial investigated adjuvant vibostolimab (anti-TIGIT) plus pembrolizumab versus pembrolizumab alone in resected stage IIB-IV melanoma. Pembrolizumab monotherapy remains a standard-of-care option in the adjuvant setting, though other established regimens (e.g., nivolumab, dabrafenib/trametinib) apply to specific subgroups. The trial highlights the need for active comparators, futility boundaries, and predictive biomarkers in future adjuvant immunotherapy studies."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • TIGIT

Rebound Growth Following Temporary Discontinuation of BRAFi and MEKi in a Patient With Multifocal BRAFV600E-Mutant Primary Brain Tumor (EANO 2026) - "At disease progression, molecular profiling identified a BRAFV600E mutation, prompting initiation of targeted therapy with dabrafenib and trametinib. This case highlights the potential for rapid "rebound growth" following even short-term discontinuation of BRAFi/MEKi therapy in BRAFV600E-mutant DLGNT. These findings suggest a strong dependence of tumor control on continuous MAPK pathway inhibition and underscore the importance of maintaining treatment continuity whenever possible. Clinicians should be aware of this phenomenon when managing therapy-related toxicities."

Clinical • Brain Cancer • Glioneuronal Tumor • Oncology • Solid Tumor

Sustained Visual Recovery with the MEKi Trametinib in an Adult Patient with Sporadic Optic Pathway Glioma Harboring a Rare BRAF Mutation (EANO 2026) - "This case emphasizes the importance of molecular profiling in OPGs to identify actionable molecular alterations (even rare) with a significant impact in restoring neurological functions."

Clinical • Astrocytoma • Brain Cancer • Glioma • Oncology • Pilocytic Astrocytoma • Solid Tumor • BRAF • NF1

Determinants of clinical decision-making in first-line treatment of pleomorphic xanthoastrocytoma and the impact of BRAF status on subsequent therapies: a 10-year single-center series (EANO 2026) - "Grade 3 PXA pts underwent multimodality treatment, with 90% (9/10) receiving either radiochemotherapy with concurrent and adjuvant temozolomide (TMZ) (n=6) or radiotherapy followed by TMZ (n=3)...Second-line systemic chemotherapies included TMZ (n=4, mPFS 3.4 months) and fotemustine/lomustine with or without procarbazine (n=3, mPFS 4.5 m). Targeted therapies administered at first or second progression included dabrafenib/trametinib (n=2, DCR 50%, mPFS 25 m), vemurafenib (n=1, DCR 100%, mPFS 27 m), and regorafenib (n=1, DCR 0%, mPFS 1.1 m)... First-line treatment for PXA is primarily driven by grade, extent of resection, and patient-related factors. Despite the high prevalence of BRAF V600E mutations, targeted therapy was utilized in a minority of cases, likely due to the long analysis period and evolving therapeutic standards, including the approval of dabrafenib/trametinib in Italy in 2024 for high-grade gliomas. The clinical impact of BRAF inhibition and its potential..."

Clinical • Astrocytoma • Brain Cancer • High Grade Glioma • Oncology • Pleomorphic Xanthoastrocytoma • BRAF

MEK Inhibition in Adult Patients with Pilocytic Astrocytomas: An Update of a Previously Published Cohort (EANO 2026) - "In this study, we provide updated results with extended follow-up from our previously reported cohort evaluating the efficacy of MEK inhibition in adult patients with PAs.Material and Methods We conducted a retrospective analysis of five adult patients (aged 30-79 years), including four with PAs and one with PA exhibiting anaplastic transformation, who were treated with trametinib, a MEK1/2 inhibitor... Despite the limited sample size, MEK inhibition demonstrated durable disease control in adult patients with PAs. These findings support MEK inhibition as a potentially effective therapeutic approach for this group of patients."

Clinical • Astrocytoma • Brain Cancer • Oncology • Pilocytic Astrocytoma • Solid Tumor • NF1

Response to nivolumab combined with dabrafenib-trametinib after extracranial metastatic escape in BRAF V600E-mutant refractory glioblastoma (EANO 2026) - "Initial management included surgical resection followed by radiotherapy (60 Gy) with concomitant and adjuvant temozolomide. Acquired resistance to BRAF/MEK inhibition represents a major therapeutic challenge in BRAF-mutant high-grade gliomas. This case highlights the potential benefit of combining MAPK inhibitors with immune checkpoint blockade in selected patients with an inflamed tumor microenvironment and high PD-L1 expression. This case expands the limited clinical evidence supporting combined MAPK inhibition and immune checkpoint blockade in this setting."

IO biomarker • Metastases • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BRAF • PD-L1

Tumor Plasticity and Adaptive Resistance: A Case of Chondrosarcomatous Transdifferentiation in Melanoma Brain Metastasis under BRAF-MEK Inhibition (EANO 2026) - "We report a striking case of BRAF-mutant melanoma exhibiting complete morphologic transformation under targeted therapy, resolved only through integrated genomic and epigenomic profiling. We report the case of a 63-year-old man with BRAF V600E-mutated cutaneous melanoma treated with the BRAF inhibitor dabrafenib (dabrafenib) and the MEK inhibitor trametinib (trametinib), whose therapy required substantial dose reductions because of toxicity. This case provides molecularly validated evidence of extreme phenotypic plasticity in BRAF-mutant melanoma brain metastasis under targeted therapy. Our findings illustrate how integrated genomic and epigenomic analyses can resolve diagnostically challenging lesions and support the hypothesis that selective therapeutic pressure may facilitate lineage reprogramming in advanced melanoma. Recognition of such plasticity is critical in the era of precision oncology, both for accurate diagnosis and for understanding mechanisms of..."

Clinical • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor

Dordaviprone (ONC201) in a pediatric patient with recurrent H3 K27M-mutant diffuse glioma and leptomeningeal disease (EANO 2026) - P | "Patients with LMD were excluded from prior response analyses due to challenges with radiographic evaluation by standard response criteria.Material and ONC028 (NCT04617002) was a US-based expanded access protocol to provide dordaviprone access to patients ineligible for clinical trials, including patients with LMD. An 11-year-old female patient with progressive right thalamic H3 K27M-mutant DMG and extensive LMD, previously treated with craniospinal irradiation (36 Gy with 18-Gy focal boost to right thalamic lesion), concurrent and adjuvant temozolomide, dabrafenib and trametinib, and a single dose of bevacizumab, was enrolled in ONC028. This case report suggests a potential role for dordaviprone use in recurrent H3 K27M-mutant DMG with LMD."

Clinical • Brain Cancer • Diffuse Glioma • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor

An ancillary study of the BIOMEDE trial using patient-derived cellular models to predict therapeutic response and disease dissemination in diffuse midline glioma (EANO 2026) - "Drug sensitivity was evaluated using viability-based assays across a panel of clinically relevant compounds including everolimus, ONC201/206, afatinib, trametinib and niraparib. This ancillary study establishes a comprehensive functional platform based on BIOMEDE-derived patient models, with the aim of enhancing and refining the biological and clinical insights generated by the trial. Ongoing molecular analyses will further characterize transcriptional programs underlying these functional phenotypes and support integrated analyses combining functional, molecular, and clinical data."

Clinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Evolution of BRAFV600E pediatric glioma tumor cell states under targeted inhibition (EANO 2026) - "To investigate transcriptomic and epigenetic evolution of tumor cell states under dual inhibition, samples were profiled using single cell RNAseq (10x genomics or FLASH-seq) and OneCell CUT&Tag. Single-cell RNA-seq and OneCell CUT&Tag analyses of BRAFV600E glioma cells treated with dabrafenib and trametinib identified two distinct populations of treatment-persistent cells, when exposed to prolonged treatment. Dual BRAF/MAPK inhibition in BRAFV600E pediatric gliomas induces divergent cell fates associated with adaptive and tolerant resistance mechanisms. The evolution of transcriptionally different population under therapeutic pressure highlights the complexity of therapeutic escape. Our data support a central role for epigenetic regulation in mediating resistance and provide a rationale for combination strategies targeting both signaling and chromatin states."

Clinical • Tumor cell • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

Impact of Neoadjuvant TKI Therapy on Tumor Reduction and Resectability in Locally Advanced Thyroid Carcinoma (ETA 2026) - "Therapies included selective (dabrafenib/trametinib, entrectinib, larotrectinib, selpercatinib) and multikinase inhibitors (lenvatinib, cabozantinib, vandetanib)... Neoadjuvant TKI therapy demonstrated promising results in locally advanced thyroid carcinoma, achieving high disease control rates and enabling surgical resection in over one-third of cases. Outcomes were comparable between selective and multikinase TKIs, and meaningful responses were observed across histological subtypes, although survival remained significantly longer in differentiated tumors. These findings, representing one of the largest single-center cohorts, reinforce the growing role of neoadjuvant therapy in multidisciplinary management of advanced thyroid cancer."

Clinical • Metastases • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Tissue-Agnostic Cancer Therapy Approvals. (PubMed, Hematol Oncol Clin North Am) - "In stark contrast to conventional cancer treatments that categorize malignancies based on their tissue of origin (eg, breast, lung, renal cell, etc), tumor-agnostic therapies transcend histologic boundaries, honing in on the genetic and molecular attributes of tumors, regardless of their location. This article offers a comprehensive review of the current landscape of tissue-agnostic cancer therapies and provides clinical insights to empower surgical oncologists with a deeper understanding of these innovative therapeutic approaches."

Journal • Review • Oncology • Renal Cell Carcinoma

Improving public cancer care by implementing precision medicine in Norway (clinicaltrialsregister.eu) - P1/2 | N=1000 | Recruiting | Sponsor: Oslo University Hospital HF | N=6000 ➔ 1000

Enrollment change • Oncology

Targeting V-Domain Ig Suppressor of T Cell Activation (VISTA) in Malignant Mesothelioma (IASLC-WCLC 2026) - "To understand and modulate key signaling pathways involved in VISTA expression, we conducted experiments treating cells with Trametinib, LY294002, capivasertib, and ruxolitinib. The IncuCyte analysis showed that both VISTA- and Mesothelin-targeted CAR T-cells at the lower E:T ratios of 0.5:1 and 1:1 led to potent killing of the MM cell lines HAY, H2461, and H2373. Conclusions : These findings offer valuable insights into the regulatory mechanisms governing VISTA-mediated immunoregulation in MM, as well as the effectiveness of VISTA- and mesothelin-targeted CAR T-cells in malignant mesothelioma."

IO biomarker • Mesothelioma • Solid Tumor • MSLN • VSIR

Marked response to dabrafenib plus trametinib in a patient with BRAF V600E-mutant pancreatic hepatoid carcinoma: a case report and systematic analysis of 57 cases. (PubMed, Front Oncol) - "After two cycles of pembrolizumab-based first-line therapy combined with paclitaxel, S-1, and lenvatinib, AFP continued to increase and imaging showed rapid tumor enlargement, consistent with immune checkpoint inhibitor-related hyperprogressive disease...Subsequent addition of cetuximab, replacement of the MEK inhibitor, and dose escalation of targeted therapy did not restore sustained systemic disease control, although local disease remained manageable with subsequent treatment adjustments...After resistance to targeted therapy, local radiotherapy may serve as an important strategy for controlling oligoresidual and oligometastatic lesions. Together with the literature review, this case supports early comprehensive molecular profiling and individualized multidisciplinary management for advanced PHC."

IO biomarker • Journal • Tumor mutational burden • Hepatocellular Cancer • Hepatology • Liver Failure • Oncology • Pain • Pancreatic Cancer • Solid Tumor • Thrombosis • AFP • BRAF • MDM2 • MGMT • MYC • PD-L1 • TMB

Dabrafenib plus trametinib in BRAF V600E-mutant Erdheim-Chester disease: a case series including CNS involvement. (PubMed, Int J Hematol) - "This case series highlights the effectiveness and tolerability of dabrafenib plus trametinib for BRAF V600E-mutant ECD, including cases with CNS and cardiovascular involvement. Molecular diagnosis and targeted therapy appear to be critical for optimizing outcomes, although further prospective studies are warranted to clarify the long-term effectiveness, resistance mechanisms, and optimal duration of this treatment approach."

Journal • Cardiovascular • CNS Disorders • Langerhans Cell Histiocytosis • Rare Diseases • BRAF • CD1a • CD68

AN R-LOOP-MODULATED MULTI-OMIC LANDSCAPE REVEALS A TUMOR-MICROBIOME-IMMUNE INTERPLAY DICTATING THERAPEUTIC VULNERABILITIES IN COLORECTAL CANCER (UEGW 2026) - "Therapeutically, high-RLscore tumors exhibited reduced sensitivity to standard chemotherapeutic agents, including irinotecan and oxaliplatin, as indicated by elevated IC50 values. Conversely, they showed increased susceptibility to MAPK pathway inhibitors, such as sapitinib, trametinib, and dasatinib... The RLscore serves as a robust, multi-dimensional biomarker, capturing the intricate interplay between tumor-intrinsic pathways, the immune microenvironment, and the microbiome in CRC. By identifying subtypes with distinct prognoses and therapeutic vulnerabilities, the RLscore provides a powerful framework for patient stratification and offers a clear rationale for personalized treatment strategies, holding significant promise for advancing precision oncology."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • CD4

Real-World Treatment Patterns and Outcomes for BRAFV600E-mutated Metastatic Non-Small Cell Lung Cancer: OCTOPUS Study (IASLC-WCLC 2026) - P | "In 1L, 37.3% (n=50) received dabrafenib + trametinib (DT; a BRAF/MEK inhibitor combination), 27.6% received pembrolizumab (P) alone (9.7%; n=13) or with chemotherapy (CT; 17.9%; n=24), 20.1% (n=27) received CT alone, and 14.9% (n=20) received other treatment types. Despite international recommendations, one-third of patients did not receive 1L or 2L BRAF/MEK inhibitor treatment, highlighting the need to optimize therapeutic strategies and treatment sequencing in patients with BRAF V600E mNSCLC. However, no definitive conclusions can be drawn due to the observational nature of this study."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

FINAL OVERALL SURVIVAL RESULTS FROM THE GOG281/LOGS STUDY EVALUATING TRAMETINIB VERSUS PHYSICIAN'S CHOICE STANDARD-OF-CARE THERAPY FOR RECURRENT LOW-GRADE SEROUS OVARIAN CANCER (LGSOC) (IGCS 2025) - P2/3 | " This international phase 2/3 trial randomly assigned (1:1) patients with recurrent LGSOC to receive either oral trametinib 2 mg once daily (n=130) or one of five SoC treatment options (n=130): intravenous paclitaxel 80 mg/m² by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40–50 mg/m² once every 4 weeks; intravenous topotecan 4 mg/m² on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. At the time of the final analysis, 29 (22.3%) patients in the trametinib arm and 15 (11.5%) patients in the SoC arm remained alive. The median OS was 36.4 months in the trametinib arm versus 29.8 months in the SoC arm (HR 0.68; 95% CI 0.49-0.94; p=0.018, 1-sided), despite the fact that 72% of patients in the SoC arm crossed over to trametinib following progression. In the 93 SoC patients who crossed over to trametinib the median PFS..."

Clinical • Late-breaking abstract • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Advances in Management of Vascular Anomalies (ASH 2026) - "Because many of these genes are established oncogenes, cancer drugs have been repurposed for these conditions, exemplified by the PI3Kα inhibitor, alpelisib, now approved for PIK3CA-related overgrowth spectrum (PROS). Ricci synthesizes the genomic landscape across phenotypes and reviews the evidence for MEK, KRAS, and BRAF inhibition, with trametinib as the most established agent. This presentation then offers a genotype-guided framework for diagnosis and management, highlighting the expanding role of the hematologist-oncologist and the barriers to delivering equitable precision care."

CNS Disorders • Rare Diseases • AKT1 • KRAS • PIK3CA • PIK3R1 • PTEN

Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2026 ➔ Sep 2027

Trial completion date • Oncology • Solid Tumor

Effectiveness of Dabrafenib plus Trametinib as second-line therapy in comparison to first-line in BRAFV600 mutated metastatic melanoma: A Real-World Analysis (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor

Pancreatic Metastases From Metastatic Papillary Thyroid Carcinoma Presenting as Acute Pancreatitis in a Patient Receiving Dabrafenib/Trametinib (ACG 2026) - "Given concern for medication-related toxicity, dabrafenib and trametinib were discontinued, and she was subsequently started on lenvatinib. This case highlights how complex pancreatic pathology underscores the importance of multidisciplinary evaluation. Figure: Figure 1: MRI abdomen/pelvis showing edematous pancreas and metastatic nodules in the pancreas"

Clinical • Metastases • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma