JCO: Tipifarnib is effective for recurrent and/or metastatic head and neck squamous cell carcinoma

In patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), the incidence of mutations in the proto-oncogene HRAS (mHRAS) is 4%-8%.
Tipifarnib is a farnesyltransferase inhibitor that can disrupt HRAS function.
This experiment evaluated the efficacy of Tipifarnib in the treatment of patients with R/M mHRAS-HNSCC.

On March 22, 2021, the Journal of Clinical Oncology published a study online.
The results showed that Tipifarnib has a significant effect on R/M mHRAS-HNSCC patients with HRAS mutations.

HNSCC accounts for more than half a million new cancer cases worldwide each year, mainly related to smoking and alcohol exposure or infection with human papillomavirus (HPV).
Although targeted therapy has recently been included in standard treatment, the prognosis of R/M HNSCC patients is still very poor, with an estimated median overall survival of 13-15 months.
Since the approval of cetuximab more than 10 years ago, the development of targeted drugs has been plagued by the limited number of drug-targetable markers and the aggressiveness of drug-resistant diseases.
The study included 22 R/M HNSCC patients with mHRAS allele mutation frequency (VAF) ≥ 20% (high VAF).
The primary endpoint of the study is the objective response rate (ORR), and the secondary endpoints include safety and tolerability.
Subjects took Tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of the 28-day treatment cycle.

The results showed that among 22 patients receiving VAF treatment, 20 patients could finally be evaluated for efficacy.

After taking Tipifarnib, the median PFS increased to 5.

This study describes the effect of Tipifarnib on the anti-tumor activity of R/M HNSCC patients.

Another striking result of this experiment is that the evaluable clinical benefit of high mHRAS VAF cured patients is 100%, which is the role of mHRAS as a tumor driver and the ability of FTIs implantation to treat tumors to provide additional evidence.

references:

Ho AL, Brana I, Haddad R, et al.

org/doi/10.