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The majority of squamocellular head and neck cancer (SCC HNC) patients presenting with advanced disease stage will eventually relapse either locoregionally and/or at distant sites.
Patients with recurrent and/or metastatic (RM) disease who are not candidates for local therapies are usually offered platinum based chemotherapy plus cetuximab, an antibody directed towards EGFR, with the goal of prolonging survival and controlling symptoms.
This combination resulted in an increase in median survival with respect to chemotherapy alone from 7.4 to 10.1 months. The addition of cetuximab also prolonged the median progression-free survival time from 3.3 to 5.6 months and increased response rate from 20% to 36% when given as first-line treatment. 1
With these premises, it should be considered that only a minority of the patients respond to chemotherapy (CT) plus cetuximab (targeted therapy, TT) thus not all SCC HN can be considered as EGFR addicted; moreover, ultimately all will develop treatment resistance to antiblastic and antiEGFR therapy.
In this context, it is crucial to better understand the molecular mechanisms involved in resistance to treatment in order: (a) to identify the patients who are likely to response to CT and TT and (b) to discover escape-alternative pathways associated with treatment resistance. This could put the basis for future trials, aimed to narrow the number of patients that are treated with a particular agent, towards a more individualized medicine. Moreover, the costs of a prolonged administration of TT are well acceptable if the treatment is efficacious, otherwise an exclusion would be desirable to avoid unnecessary toxicity.
From a pharmacoeconomic point of view, cetuximab added to platinum based chemotherapy in RM setting showed an high incremental cost-effectiveness ratio per quality-adjusted life-year gained, prompting some national regulatory authorities not to pay for antiEGFR therapy in RM SCCHN 2, thus adding importance to recognition of therapeutic sensitivity.
In contrast with other tumors, no recognized biological factors have been identified as predictive biomarkers of response either to CT or to TT with antiEGFR drugs. EGFR copy number status was neither predictive of tumor response to cetuximab, nor prognostic factor, as demonstrated by a recent analysis of tumor specimens of patients involved in Extreme trial.3 Different predictive biomarkers for EGFR-targeted therapies have not yet been discovered nor validated in this setting of disease.
A small percentage of patients achieves long term response with CT and TT combination, with clinical benefit lasting more than 1 year. We are very interested in studying this subset of patients, in order to generate hypothesis about predictive clinical and molecular variables, through different molecular analysis.