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Targeted therapy selection-based on tumor tissue kinase activity profiles in patients with refractory solid tumors: An exploratory study.

e21080 Background: Clinically applicable response prediction tools are urgently needed to optimize treatment selection for individual patients. We designed an exploratory study to determine feasibility and clinical benefit of treatment with clinically available kinase inhibitors (KIs) selected by kinase activity profiling, performed in lysates of fresh-frozen tumor biopsies from patients with solid malignancies refractory to standard treatment. We here report the preplanned feasibility analysis.


METHODS
From September 2010 thirteen patients were enrolled in this ongoing study for treatment selection between dasatinib, erlotinib, everolimus, lapatinib, sorafenib and sunitinib according to a standardized method. At first, from a mandatory, snap-frozen tumor needle biopsy multiple 10 µm cryosections are prepared, with conventional H&E staining of 2 sections every 0.25 mm to determine tumor cell content. If these reveal more than 50% tumor cells, remaining sections are lysed. In this lysate the inhibitory potency of a KI is determined by using a peptide-based array of PamGene with 144 tyrosine kinase substrates. Based on the number of significantly inhibited substrates and percentage inhibition, the most potent KI is selected for treatment of the individual patient. Treatment response is evaluated according to RECIST criteria.


RESULTS
Thus far, per patient a median of 3 biopsies with a median size of 16G were taken from a metastatic site guided by US in 77%. In 92% of patients at least one biopsy contained sufficient tumor cells; 1 patient required re-biopsy. Lysates yielded 636 ±254 µg protein (range 247-1188). Following kinase activity profiling in 12 patients, 11 started treatment with a selected KI. To date 6 patients were evaluable, showing 1 SD and 5 PD at 6 weeks. Two patients were not evaluable due to early clinical deterioration.


CONCLUSIONS
We here show that needle biopsies from metastases of refractory solid cancer patients provide sufficient protein to reliably determine kinase inhibition profiles of KIs. Patient accrual and updated clinical benefit data will be presented at the meeting.