Abstract: PD04-12
Sources of Funding: none

Introduction

Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for metastatic renal cell carcinoma (mRCC), with up to 20% of tumours exhibiting de novo resistance to TKIs. At present, there is no method of predicting response to systemic targeted therapy. We present a descriptive study of a prospective cohort of mRCC patients & the correlation of clinical outcomes to the responses predicted by patient-derived xenograft (PDX) models using the ex-ovo avian embryo.

Methods

We prospectively collected demographic, pathologic, & clinical data on 26 patients with mRCC undergoing cytoreductive nephrectomy. PDX models were tested in 5 patients. Six core biopsies were taken from each primary tumor. Cores were sectioned & engrafted directly onto embryonic day 9 chorioallantoic membranes (CAMs) of avian embryos & treated with topical sunitinib or a DMSO control. On day 6 post-engraftment, Doppler & contrast-enhanced ultrasound were performed to assess vascularity & perfusion of tumours grown on the CAM models. A composite vascularity & perfusion score was obtained and used to determine the presence or absence of a response to TKIs compared to the control. Tumours were considered TKI-sensitive if there was a response in ≥4 cores. Tumours with responses in ≤3 cores were considered TKI-resistant. Clinical progression on CT scan was based on RECIST criteria.

Results

Results are summarized in Table 1. All tumours demonstrated heterogeneous responses to TKIs in the PDX model. Using the criteria of ≥4 cores responding to TKI therapy, we would expect a good response in patient 3, who does not have evidence of clinical progression after 5 months of maintenance on sunitinib. Moreover, patient 3 had 3 cores engrafted from a metastatic deposit, which all responded well to sunitinib in the PDX model. Patients 1 & 2 continued to show signs of progression despite switching to alternative agents, and both have discontinued systemic therapy due to intolerable side effects or enrolment in another clinical trial respectively. Patients 4 & 5 have not started on systemic targeted therapy.

Conclusions

Further studies in a larger population are warranted to explore the potential of the PDX model to serve as a novel phenotypic biomarker in the prediction of targeted therapy tumor resistance in RCC.

Funding

none