HRAS mutations are found in head and neck cancer (HNC) as putative oncogenic drivers.
Incidence of HRAS mutations was 4% in TCGA cohorts, and 8% in other screening cohorts.
Tipifarnib is a well-known farnesyl transferase inhibitor and was mainly developed
as an anti-cancer agent in leukemia therapy. Recently, it proved to be a highly selective
inhibitor of HRAS-driven de-differentiated thyroid cancers.
We report on two cases of HNC patients, one squamous cell carcinoma of the oral cavity
and one epithelial-myoepithelial carcinoma of the parotid gland. Both patients are
in a palliative situation due to progressive metastatic disease after combinatory
cytostatic and immunotherapeutic treatments. The patients underwent a HNC biomarker/panel-sequencing
program, which was designed by our institution. Furthermore, a Cancer Hotspot Panel
addressing mutations of genes like BRAF, HRAS or SMARCB1 was performed. We could detect
canonical HRAS mutations and having no other treatment options both patients were
referred to a named-patient program including tipifarnib therapy.
Up to now, both patients show partial response to the therapy with rapid and durable
significant reduction of tumor volume and tolerable side effects.
Regarding the literature, HRAS mutations are frequently found in HNC, especially in
salivary gland cancer. Thus, tipifarnib might be a promising agent for this subgroup
of patients, which can be identified by molecular analysis. A phase IIb study on tipifarnib
treatment in recurrent and metastatic HRAS-mutated HNC is currently initialized at
our Early Clinical Trial Unit.
