MDM2 loss is associated with patient response to PalbociclibSeven patients with measurable advanced WD/DDLS confirmed positive for CDK4 amplification and Rb protein expression, and whom had progressed on at least one systemic therapy prior to enrollment (clinicaltrials.gov identifier NCT01209598), consented to pre-treatment biopsies taken prior to therapy and post-treatment biopsies taken after receiving one dose of oral PD0332991 (125mg daily for 21 days). Tumor response was assessed with CT scan by a reference radiologist every 6 weeks for 36 weeks, and every 12 weeks thereafter. Patients were followed up until March 2014. Three patients (red bars) did not derive clinical benefit and stopped treatment within 84 days. Two of these patients (#2 and #3, triangles) died on study and are indicated with a triangle. The third patient, #8, came off study as their disease progressed. Four patients (blue bars) had demonstrable clinical benefit, remaining on treatment for more than 84 days. Two of these progressed after 168 (#8) and 376 (#7) days respectively, while two remained on treatment with ongoing benefit (arrows), one achieving a complete response (star). (Inset) Extracts were prepared from pre- and post-treatment biopsies of protein expression measured by immunoblot. GAPDH was a loading control.
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