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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.
Abstract:
PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9-24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients.
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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