ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This article reports a successful medical trial to test the therapeutic potential of targeting the BRAF-MEK pathway (using vemurafenib-cobimetinib combination therapy) in 16 patients with newly diagnosed papillary craniopharyngiomas (PCPs).

The authors recruited 16 patients with PCP who tested positive for BRAFV600E mutation, had not undergone radiation therapy and had measurable disease. The primary endpoint was objective response at 4 months using volumetric data. Importantly, 15/16 PCP patients showed a partial response with a reduction of 91% of the tumour volume.

PCP tumours, although benign, are challenging to treat due to their critical location near the hypothalamus and optic chiasm, often resulting in significant morbidity post-surgery. This study examined the efficacy of combined BRAF and MEK inhibitors (dabrafenib and cobimentinib), known to be successful in other BRAF-mutant cancers, including melanoma and thyroid cancer. It found promising results, with significant tumour shrinkage observed in patients treated with the combination therapy. The treatment modality was cycles of 28 days with patients receiving vemurafenib (960 mg orally twice daily) and cobimetinib (60 mg orally once daily) for 21 days. The primary endpoint objective response was assessed by central radiologic review of pre-specified volumetric criteria by MRI every 8 weeks. Secondary endpoints were progression-free survival, response defined by enhancing volume and adverse events. This treatment strategy represents a potential paradigm shift in managing papillary craniopharyngiomas, moving away from the traditional reliance on surgery and radiation, which often lead to long-term complications.

Clinical implications: This study indicates that targeted therapy using BRAF-MEK inhibitors may offer a less invasive and more effective option for patients with newly diagnosed PCPs, potentially preserving neurological function and improving quality of life. However, further studies are needed to assess long-term outcomes, progression of the disease after treatment and confirm the broader applicability of this treatment approach in a larger cohort of patients.