Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations

Area of Science:

• Oncology
• Molecular Biology
• Clinical Trials

Background:

• Mutations in the HRAS proto-oncogene are found in 4%-8% of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
• Tipifarnib, a farnesyltransferase inhibitor, targets HRAS function, offering a potential therapeutic strategy for HRAS-mutated cancers.

Purpose of the Study:

• To evaluate the efficacy and safety of tipifarnib in patients with R/M HNSCC harboring HRAS mutations.
• To assess the objective response rate (ORR) as the primary endpoint in this patient population.

Main Methods:

• A single-arm, open-label Phase II trial enrolled 30 patients with R/M HNSCC.
• Enrollment criteria were refined post-hoc to include patients with a high variant allele frequency (VAF) of HRAS mutations (≥20%).
• Patients received tipifarnib at 600 or 900 mg orally twice daily in 28-day cycles.

Main Results:

• Among 20 evaluable patients with high-VAF HRAS-mutated HNSCC, the ORR was 55% (95% CI, 31.5 to 76.9).
• Median progression-free survival (PFS) was 5.6 months with tipifarnib, compared to 3.6 months with prior therapy.
• Median overall survival (OS) was 15.4 months. Common adverse events included anemia and lymphopenia.

Conclusions:

• Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC and HRAS mutations.
• The drug offers a potential treatment option for patients with limited therapeutic alternatives.
• Further investigation in HRAS-mutated HNSCC is warranted.