AACR-NCI-EORTC: Activity of Tipifarnib in Patients With HRAS-Mutant Head and Neck Squamous Cell Carcinoma

Get Permission

A small phase II study investigating the efficacy and safety of the investigational farnesyl transferase inhibitor tipifarnib in patients with recurrent and metastatic HRAS-mutant head and neck squamous cell carcinoma found the agent produced objective responses in the patient population. Based on the study’s results, a pivotal study evaluating the efficacy of tipifarnib in HRAS-mutant head and neck squamous cell carcinoma has been initiated. The study by Ho et al was presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Abstract PR08). The conference is jointly provided by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Organisation for Research and Treatment of Cancer (EORTC).

Recurrent and metastatic neck squamous cell cancer is usually incurable, and median survival is generally poor—between 6 and 15 months, depending on patient- and disease-related factors. According to information in the AACR Project GENIE database, HRAS mutations are found in about 4% of head and neck squamous cell carcinomas.

Study Methodology

Overall, 23 patients with head and neck squamous cell carcinoma and 10 patients with squamous cell carcinoma of other histologies were treated with tipifarnib. The patients had relapsed or refractory disease and a median of two prior treatment regimens. The researchers noted that no objective partial responses were observed on the patients’ last therapy prior to entry into the study, including platinum therapy, immunotherapy, or cetuximab, with or without chemotherapy.

The patients received 600 to 900 mg of oral tipifarnib twice daily on days 1 through 7 and days 15 through 21 of 28-day cycles.


  • Tipifarnib showed clinical activity in patients with recurrent and metastatic head and neck squamous cell carcinoma harboring a HRAS genetic mutation.
  • The agent was safe and well tolerated in patients who have received multiple prior therapies.

Study Results

The researchers found that among the 15 patients with head and neck squamous cell carcinoma meeting the HRAS mutation–high variant allele frequency inclusion criteria, the overall response rate was 53%, which included eight partial responses and five patients with stable disease. Two patients await first on-study tumor response assessment.

The overall median progression-free survival in patients with high variant allele frequency (20% or higher) was 5.4 months; 19 months for those with a partial response; and 4.5 months for patients with stable disease. In contrast, no objective responses were seen on the patients’ last prior therapy, with a median progression-free survival of 3.2 months.

All patients treated with tipifarnib had at least one treatment-emergent adverse event. The most frequently observed treatment-emergent adverse events greater than grade 3 were blood and lymphatic system disorders, gastrointestinal disorders, and renal disorders.

Potential Clinical Relevance

“Tipifarnib may represent a promising new therapy for [patients with] HRAS-mutant head and neck squamous cell carcinoma,” said lead study author Alan L. Ho, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, in a statement. “The success of the trial also speaks to the promise of utilizing genomic sequencing of diseases to identify highly effective therapies that are personalized to the specific biology of each individual patient’s tumor.”

Disclosure: The study was funded by Kura Oncology. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.