Tafinlar (dabrafenib)

Targeted therapy with dabrafenib and trametinib was initiated, resulting in rapid clinical improvement and complete wound healing. Adult chest wall LCH represents a rare diagnostic challenge due to its malignant radiographic appearance. Histopathologic confirmation, with molecular testing, is essential, and targeted BRAF/mitogen-activated protein kinase kinase (MEK) inhibition may provide an effective therapeutic option when conventional measures fail.

Therapeutic targeting of BRAFV600E has led to the approval of dabrafenib plus trametinib for solid tumours [excluding colorectal cancer (CRC)] refractory to standard therapies...In CRC, intrinsic epidermal growth factor receptor (EGFR) activation circumvents BRAF inhibition, necessitating the concurrent use of EGFR inhibitors, whose treatment strategy led to the approval of encorafenib plus cetuximab for BRAF V600E CRC...While noteworthy results have been achieved with BRAFV600E inhibition, further research is needed to optimize BRAF-targeted therapies and address resistance mechanisms. Continued research and innovation are crucial to improving patient outcomes and addressing the complexities of BRAF mutations in human cancers.

P4, N=165, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jun 2026 --> Nov 2026

Genetic testing identified a BRAF mutation, which led to the initiation of targeted therapy using dabrafenib in combination with trametinib. Therefore, implementing rigorous postoperative patient education and follow-up protocols is key to the early detection of recurrence and timely intervention. Simultaneously, the present case illustrates the challenge of acquired resistance to targeted therapy, underscoring the importance of developing strategies to overcome such resistance to potentially improve patient survival in the future.

P1/2, N=57, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Jun 2030 --> Mar 2026 | Trial primary completion date: Mar 2027 --> Mar 2026

Tislelizumab can induce fulminant type 1 diabetes via immune-mediated mechanisms. Proactive monitoring of fasting glucose, HbA1c, and islet function is essential for patients with cancer receiving tislelizumab therapy.

P1/2, N=16, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 16 | Trial completion date: Nov 2025 --> Jan 2027

P4, N=165, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

The patient began treatment with dabrafenib-trametinib, followed by pembrolizumab as second-line therapy, ultimately extending her life by nearly seven months. The complexities of accessing newer therapies in Canada's single-payer healthcare system are also emphasized. The utilization of newer rapid diagnostic technologies can have a direct impact on directing treatment for ATC and other aggressive malignancies.

Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.

Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival.