A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer

Abstract

Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic.

Figure 1

Clinical outcome of patient CBI-0803 and response to anticancer agents in patient’s xenografts. A, time course of CEA levels. B, tumor growth curve of patient’s personalized tumorgraft, treated with the indicated agents at the dose and schedules. C and D, CT scan of the abdomen, before and after treatment with irinotecan-cetuximab and bevacizumab, showing a marked decrease in tumor volume. E, tumor growth curve of patient’s tumor treated with the indicated agents.

Figure 2

Clinical outcome of patient CBI-0805 and remarkable antitumor potential of irinotecan in patient’s xenografts. A, response of patient’s tumorgraft to single-agent irinotecan illustrates a complete eradication of the tumor. B, CT scan of pelvis before treatment. C, CT scan of pelvis showing a significant reduction in a metastatic pelvic mass. D, intratumor concentration of irinotecan and SN38 in this patient’s xenograft and an irinotecan-resistant colorectal cancer (CRC) tumorgraft (CRC-005), showing heightened retention of SN38 in CBI-0805.