Conclusion
Loss of PTEN expression may be associated with lack of benefit from cetuximab. This analysis is limited by small sample size, and PTEN as a potential predictive biomarker merits validation in larger sample sets.
Methods
Tumor PTEN and PIK3CA/PI3K p110α were analyzed in samples from subjects treated on two trials of cetuximab-based therapy for patients with metastatic or recurrent HNSCC: E5397, a randomized trial of cisplatin plus placebo versus cisplatin plus cetuximab; and NCI-8070, a randomized trial of cetuximab plus sorafenib versus cetuximab. In situ quantification of PTEN and PI3K p110 α was performed using the AQUA™ method of quantitative immunofluorescence. PI3KCA hot spot mutations were determined with BEAMing.
Results
For E5397, in multivariable analysis, PTEN expressing/PIK3CA WT patients tended to improve PFS with cetuximab compared to placebo (N = 48; HR = 0.54, Wald p = 0.0502). High PTEN expression was significantly associated with superior PFS among patients treated on NCI-8070 (N = 37; HR = 0.35, p = 0.008).