In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 6011-6011
Abstract:
6011 Background: PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal SCC (OPSCC), with a prevalence of 20-30%. While PIK3CA mutations have been associated with adverse outcomes in cervical cancer, their prognostic significance in HPV-associated OPSCC remains unknown. We sought to elucidate the significance of PIK3CA mutations in a prospective cohort of HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Methods: Seventy-eight patients with HPV-associated OPSCC were prospectively enrolled on three protocols: LCCC 1121 (NCT03161821) or two phase II clinical trials of de-intensified CRT (NCT02281955 / NCT03077243). De-intensified regimen was 60 Gy IMRT with concurrent cisplatin (30mg/m 2 ). Next-generation sequencing of tumor samples was performed using a targeted panel-based assay (UNCSeq), including over 200 genes. We estimated disease-free survival (DFS) using the Kaplan-Meier method and compared treatment groups with two-sided log-rank test (Medcalc). Results: Sequencing was performed in 78 patients with a median follow-up of 24 months. Seventy-five patients received 60Gy; three patients received 70Gy. Ten patients had disease recurrence (2 regional only, 5 distant only, 3 regional and distant). Thirty-eight of 78 patients had at least one mutation identified (17 PIK3CA, 4 PTEN, 3 KRAS, 3 FBXW7, 3 FGFR3, 2 TP53, 2 prothrombin 20210, 1 NRAS, 1 BRCA1, 1 factor V Leiden, 1 FLT3, 1 RAD50, 1 PIK3R1). The most common site of PIK3CA mutation was the helical domain (E545K – 8/17, E542K – 2/17). Despite similar T/N staging and tobacco pack years, patients with WT-PIK3CA had significantly higher DFS (93%) compared with 65% for patients with PIK3CA mutations (p = 0.0009). Patients with mutations other than PIK3CA also had improved DFS relative to those with PIK3CA mutations (96% vs. 65%; p = 0.0147). Conclusions: PIK3CA mutation is associated with worse DFS in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with definitive CRT. These findings suggest that patients with PIK3CA mutations may not be suitable for de-intensified therapy and investigation of novel treatment strategies may be appropriate.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.6011
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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