Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma

Julie A Theurer1,2,3,4, William Stecho5, John Yoo6,7,8

  • 1Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, 800 Commissioners Rd. E., London, ON, N6A 5W9, Canada. jtheurer@uwo.ca.

Insights

Activating PIK3CA mutations occur in 16% of head and neck cancers. Patient interest and timely detection support launching targeted PIK3CA drug trials in single institutions.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Trials

Background:

  • PIK3CA is a frequently mutated, druggable oncogene in head and neck squamous cell carcinoma (HNSCC).
  • Launching molecularly-driven trials in HNSCC faces challenges including mutation detection infrastructure, prevalence, and patient willingness.
  • A single-institution setting requires evaluating these factors for feasibility.

Purpose of the Study:

  • To assess the local frequency of PIK3CA activating mutations in HNSCC.
  • To evaluate the timeliness of the mutation-profiling clinical pathway.
  • To gauge patient willingness to enroll in a novel neoadjuvant PIK3CA-targeted drug trial.

Main Methods:

  • Real-time PCR was used to test 25 HNSCC tissue biopsies for PIK3CA mutations at three hotspots.
  • Mutation prevalence and turnaround time (working days) were calculated.
  • Prospective surveys assessed the willingness of 30 HNSCC patients to join a hypothetical trial.

Main Results:

  • PIK3CA activating mutations were identified in 4 of 25 (16%) HNSCC tumors.
  • Mutation status was determined in an average of 15 working days (range: 9-24).
  • 70% of surveyed patients expressed willingness to participate in a PIK3CA-targeted trial.

Conclusions:

  • PIK3CA activating mutations occur at a significant frequency in HNSCC.
  • The mutation-profiling pathway demonstrated sufficient timeliness for clinical trial initiation.
  • Sufficient patient interest exists to support a targeted PIK3CA intervention trial in HNSCC.

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