Low PTEN expression is associated with worse overall survival in head and neck squamous cell carcinoma patients treated with chemotherapy and cetuximab
- 415 Downloads
Platinum-based chemotherapy associated with cetuximab is the first-line treatment for inoperable recurrence or metastatic head and neck squamous cell carcinoma (HNSCC). There is no established biomarker for cetuximab efficacy in HNSCC. The PI3K pathway is one of the most frequently altered pathways in HNSCC. Loss of phosphatase and tensin homolog (PTEN) expression occurs in up to 30 % of cases.
This was a retrospective analysis of data from 61 patients with inoperable recurrence or metastatic HNSCC treated with cetuximab. PTEN, epidermal growth factor receptor and p16 expression were analyzed by immunohistochemistry and tested for association with clinical outcomes.
Median overall survival was 11.4 months and progression-free survival was 6.9 months. Low PTEN expression was present in 26.2 % of patients and identified patients with worse prognosis. p16 was positive in only 8.5 % of tumors.
Low PTEN expression in patients treated with cetuximab plus chemotherapy emerged as a prognostic biomarker and should be evaluated for its predictive role for cetuximab efficacy.
KeywordsPTEN p16 Cetuximab Head and neck cancer Biomarker Prognosis
Conflict of interest
All authors declare they have nothing to disclose.
- 16.Pectasides E, Fountzilas G, Kountourakis P et al (2010) Evaluation of the incidence and prognostic value of mutant epidermal growth factor receptor (EGFRvIII) protein expression in head and neck squamous cell carcinomas (HNSCC) using AQUA. J Clin Oncol 28(15 suppl):5538Google Scholar
- 17.Licitra L, Mesia R, Rivera F et al (2011) Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol 22:1078–1087CrossRefPubMedCentralPubMedGoogle Scholar
- 18.Licitra L, Störkel S, Kerr KM et al (2013) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer 49(6):1161–1168CrossRefPubMedGoogle Scholar
- 22.Cohen EEW (2011) Reply to D. Herchenhorn et al. J Clin Oncol 29:e285–e287Google Scholar
- 33.Vermorken JB, Stöhlmacher-Williams J, Davidenko I et al (2013) Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol 14:697–710CrossRefPubMedGoogle Scholar
- 40.Pfisterer K, Fusi A, Klinghammer K et al (2014) PI3K/PTEN/AKT/mTOR pathway genetic variations are associated with the clinical outcome in patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment. Head Neck (in press). doi: 10.1002/hed.23604
- 42.Perez EA, Dueck AC, McCullough AE et al (2013) Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial. J Clin Oncol 31:2115–2122CrossRefPubMedCentralPubMedGoogle Scholar
- 44.Jerusalem G, André F, Chen D et al (2013) Evaluation of everolimus (EVE) in HER2+ advanced breast cancer (BC) with activated PI3K/mTOR pathway: exploratory biomarker observations from the BOLERO-3 trial. Eur J Cancer 49(Suppl 3):proffered papers session LBA16 p S6Google Scholar
- 45.Yokota T (2014) Is biomarker research advancing in the era of personalized medicine for head and neck cancer? Int J Clin Oncol 19(2):211-9. doi: 10.1007/s10147-013-0660-4
- 47.Vermorken JB, Psyrri A, Mesía R et al (2013) OP041: impact of human papillomavirus (HPV) and p16 status on survival and response with cisplatin plus 5-FU and cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): analysis of the phase III extreme trial. Oral Oncol 49(Suppl 1):S19–S20. ISSN 1368-8375Google Scholar