Mekinist (trametinib)

P2, N=52, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

This case series highlights promising outcomes with systemic treatment options in ATC, but the analysis is limited by a small sample size, emphasising the need for further research and collaboration to improve clinical outcomes.

MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.

Combining targeted therapies with immune checkpoint inhibitors showed promising results in two patients with advanced BTC driven by specific genetic mutations. Significant tumor reduction and successful surgeries suggest this approach may improve resectability and outcomes. These cases highlight the potential of personalized treatment guided by genetic profiling. Further research is needed to confirm these findings and explore broader applications for this strategy.

Conventional radiotherapy combined with temozolomide proved ineffective. This is the first reported case of multi-oncogenic pathway alterations following BRAF-targeted therapy in PXA. These genetic abnormalities likely contributed to the tumor's drug resistance and aggressive progression in this case.

Our findings underscore the prognostic value of the identified genes and the immunosuppressive TME in TP53-mutant breast cancer. The identification of drug candidates with strong binding affinities to key proteins provides promising avenues for targeted therapy in this high-risk patient population.

Trametinib is useful in NRAS-driven leptomeningeal melanoma in children, but not sufficient to prevent relapse, and can be helpful in NRAS-driven leptomeningeal dysplasia. It is very helpful symptomatically in BRAF fusion-driven cutaneous disease, where a reduced dose after initial response appears to sustain efficacy and reduce adverse effects.

P3, N=603, Active, not recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 --> Jan 2026

This exploratory analysis suggests pERK expression and mutation of KRAS/BRAF/NRAS are candidate biomarkers of improved PFS and response to trametinib, respectively.

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

MEK inhibition with trametinib resulted in similar, yet more pronounced effects. Thus, our findings provide novel insights into NRAS-mediated signaling through nanoscale clusters and underscore their potential as therapeutic targets.

P2, N=200, Completed, Melanoma Institute Australia | Active, not recruiting --> Completed | N=1000 --> 200 | Trial completion date: Dec 2028 --> Dec 2025