Abstract B32: Retrospective correlative study between EGFRvIII, HPV, p16, c-MET and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)
Bibliographic record
Abstract
Abstract Background: No validated biomarkers exist to predict the response to EGFR inhibitors in SCCHN. A constitutively activated mutant, EGFRvIII, confers oncogenicity in human cancers and resistance to EGFR blockade, and is detected in 42% of 33 SCCHN tumors (Sok et al. Clin Cancer Res 2006). The aim of this study is to confirm the prevalence of EGFRvIII, HPV, p16, c-MET in R/M SCCHN and evaluate their potential prognostic and predictive role. Materials and Methods: Archival tumor specimens of 53 patients (pts) who were treated in 4 phase I/II trials for R/M SCCHN at Princess Margaret Hospital from 2000–2005 were examined. Two of the 4 trials involved the EGFR inhibitor erlotinib (tumor specimens available in 35 of 48 pts) whereas the remaining 2 trials involved non-EGFR targeted agents (tumor specimens available in 18 of 37 pts). EGFRvIII mutation was determined by quantitative RT-PCR (positive result determined by decreased expression of exon 4 compared with exon 9 of the EGFR gene), presence of HPV DNA by Linear Array Genotyping, p16 and c-MET expression by immunohistochemistry, using p16CINtec (Westborough, MA) and SP44 (Ventana, Tuczon, AZ) antibodies, respectively. Results: Demographics of the 53 pts were: median age 56 (range 15–78), F:M (%) = 23:77, ECOG 0:1:2 (%) = 28:64:8, locoregional recurrence = 85%, metastatic disease = 36%, oropharyngeal primary = 38%. Overall response rate (CR+PR) of the entire cohort to study treatment = 4/53 (7.5%), median TTP = 1.8 months, median OS = 5.9 months. Univariate analyses were significant for erlotinib-treated pts compared to non-erlotinib treated pts in both TTP and OS. EGFRvIII was detected in 22 pts (42%); median fold change was 6.8 (0.56–576.36). The presence of EGFRvIII mutation was associated with better disease control (PR+SD) on univariate analysis (p = 0.01), but no difference was seen between erlotinib-treated versus non-erlortinib treated pts. Median EGFRvIII fold changes were higher for pts with PR+SD than pts with PD (11.11 vs 3.16, p=0.04). The presence of EGFRvIII mutation was not associated with TTP or OS. HPV DNA (16, 6 or 33) was detected in 20 pts (38%), p16 immunostaining was present in 17 pts (32%) and c-MET was highly expressed (IHC score >2) in 31 pts (58%). HPV, p16 and c-MET were not associated with response, TTP or OS. Conclusions: This retrospective study confirms the presence of EGFRvIII mutation in about 40% of SCCHN, and it appears to be a prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Interestingly, the presence of activating mutations conferring a better prognosis has been reported with EGFR mutations in NSCLC (Eberhand et al. J Clin Oncol 2005) and with PIK3CA mutations in breast cancer (Kalinsky et al. Clin Cancer Res 2009). The positive prognostic value of EGFRvIII in R/M SCCHN is unexpected and large prospective studies are required to validate its significance. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B32.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".