Anti-EGFR target therapy in advanced thymic epithelial tumors.

Abstract

8567 Background: Thymic epithelial tumors (TETs), show a high rate of EGFR immunohistochemistry (IHC) positivity, however, the prognostic and predictive role of EGFR has not yet been well defined, and contradictory data have emerged regarding the delivering of anti-EGFR monoclonal antibodies in TETs. The outcomes of the largest series of thymoma patients treated with cetuximab, and its hypothetic immune-modulatory role, are here described. Methods: Seven patients with diagnosis of pre-treated advanced thymoma and score positivity 2+ and 3+ at EGFR-IHC, were treated with cetuximab as off-label modality, with a dose of 400 mg/m2 in the first cycle and 250 mg/m2 in the following cycles every 7 days, until disease progression, unacceptable toxicity, withdrawal of consent. Primary endpoint was Overall Response Rate ORR, assessed radiologically. Secondary endpoints were progression Free Survival (PFS), safety, and relationship between time to cetuximab progression (TTPc) and time to previous treatment progression (TTP1). During treatment with cetuximab lymphocyte subpopulations have been carefully monitored in 4 patients affected by both thymoma and Good syndrome (GS) defined as B-cell lymphocyte counts (CD19+) <100 cells/mm3 and/or Immunoglobulin G (IgG) levels <8 g/L. Results: With a median response duration of 17 months, a partial response was achieved in five patients (ORR=71%). Statistically significant correlation was found between disease response and EGFR-IHC score 2+ vs 3+ (P, .008), which statistically correlated also with the mPFS of 14 months (95% CI, 0.0-34.5). No grade 3 or 4 adverse events were registered. TTPc was longer than TTP1 in 6/7 patients (86%), with a TTPc / TTP1 ratio equal to 2.12. During cetuximab treatment, in the longest responder patient affected also by GS, a progressive increase of IgG level and of CD4/CD8 ratio has been registered as well as an increase of both CD19+lymphocytes and CD16+ 56+ lymphocytes has been detected in all the included patients with GS. Conclusions: Despite of the small number of patients and the off-label treatment modality, the data presented are worthy of confirmation in validated prospective studies in selected population with hyper-expression of EGFR. Further studies are also needed for deeply investigate the immunomodulatory role of cetuximab which seemed to temporarily revert sever immunodeficiency in our population.