Lenvima (lenvatinib)

P1/2, N=230, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Nov 2026 --> Jun 2027

P1/2, N=301, Active, not recruiting, Eisai Inc. | Recruiting --> Active, not recruiting | Trial completion date: Aug 2027 --> Mar 2027 | Trial primary completion date: Aug 2027 --> Mar 2027

P2, N=30, Active, not recruiting, Massachusetts Eye and Ear Infirmary | Trial completion date: Nov 2026 --> May 2026 | Trial primary completion date: Oct 2025 --> May 2025

Therapies using tyrosine kinase inhibitors, such as sunitinib and newer drugs (lenvatinib, surufatinib, cabozantinib), may partially normalize the tumor's disrupted vascular architecture and thus increase its susceptibility to immunological interventions. In the coming years, it will be crucial not only to overcome the immunosuppressive nature of the TME but also to identify predictive biomarkers that will allow for more precise patient selection. This approach may open the way to more effective, personalized therapies for pNENs.

Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement.

Despite disease progression, a combination of lenvatinib and pembrolizumab has shown recent stabilization. This case underscores the importance of genomic profiling in identifying rare RCC subtypes and guiding treatment decisions. Given the aggressive course and lack of established guidelines, further research is needed to optimize therapeutic strategies for these molecularly defined RCC variants.

P2, N=30, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P3, N=1069, Active, not recruiting, Eisai Inc. | Trial completion date: Mar 2026 --> Mar 2027

P1/2, N=80, Recruiting, IRCCS Istituto Nazionale Tumori Fondazione Pascale | Not yet recruiting --> Recruiting

Increased vigilance is required when combined with lenvatinib due to higher thyroid dysfunction risk. Overall, pembrolizumab remains an effective and well-tolerated option across diverse cancers, underscoring the importance of careful patient selection and close monitoring to optimize therapeutic outcomes.

By blocking the mechanisms that lead to angiogenesis and tumor growth, first-line systemic treatments, such the multi-tyrosine kinase inhibitors (TKIs) lenvatinib and sorafenib, have shown moderate improvements in survival. However, their long-term efficacy is significantly reduced by intrinsic and acquired resistance, which is why second-line medications like regorafenib, cabozantinib, and ramucirumab are being studied. When combined with anti-VEGF treatments, parallel developments in immunotherapy, in particular immune checkpoint inhibitors (ICIs) such as atezolizumab and nivolumab, have shown promising outcomes...In the end, the review promotes the combination of dynamic molecular profiling and biomarker-driven precision medicine to enhance patient stratification, improve treatment decision-making, and provide long-lasting clinical effects. A strategic foundation for future advancements and individualized treatment of hepatocellular carcinoma is provided by this comprehensive synthesis.

P=N/A, N=120, Recruiting, Fujian Medical University