The rare cancer chordoma affects one in a million people. The existing primary treatments are surgery and radiation, and no systemic therapies are currently approved for advanced chordoma. The aim of the present study was to test the efficacy of afatinib and palbociclib (epidermal growth factor receptor [EGFR] and CDK4/6 inhibitors, respectively) in three patient-derived xenograft (PDX) mouse models of chordoma as either individual agents or a combination. The study endpoints were when the control group reached mean tumor volumes (TV) = 1500 mm3 or at the end of 42 days. Statistically significant reductions in TV were seen in the CF538 PDX model in the drug combination-treated animals as compared to untreated control and single agent treatment (untreated vs. afatinib and palbociclib, p value = 0.0057) and (palbociclib vs. afatinib and palbociclib, p value = 0.0031), respectively. This study identified a combination strategy that can potentially benefit a subset of chordoma patients.
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