The study reviewed the results of 67 patients from institutions across Brazil. Tumor samples were transported by overnight courier to California for drug response profiling. A broad array of tumors were included. The overall success rate provided actionable results in 62 of 67 patients (92 percent). More than 75 percent of the studies provided results for between 8 and 16 drugs and combinations with a median of 12 reported. Several strikingly good responses were observed, including novel combinations identified in the laboratory. This study confirms the feasibility of international collaboration and reflects the globalization of medical care delivery.
International collaboration in personalized medicine for the treatment of advanced and drug-refractory cancers: Clinical application of human tumor primary culture analyses.
Subcategory: Cytotoxic and Other Novel Agents
Session Type and Session Title: This abstract will not be presented at the 2013 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: e13562
Citation: J Clin Oncol 31, 2013 (suppl; abstr e13562)
Author(s):
Fabricio Colacino Silva, Fernando C. Maluf, Antonio C. Buzaid, Robert Alan Nagourney, Nise Hitomi Yamaguchi, Paulo D'Amora, Steven Evans, Paula J Bernard, Federico Francisco; Hospital do Cancer Alfredo Abrao, Campo Grande, Brazil; Hospital Sirio-Libanes, São Paulo, Brazil; Hospital São José, São Paulo, Brazil; Rational Therapeutics, Long Beach, CA; Institute of Advances in Medicine and Hospital Albert Einstein, Sao Paulo, Brazil; Centro de Genomas, Sao Paulo, Brazil
Background:
Personalized oncology has advanced through genomic and proteomic platforms. BCR-abl; EGFr and ALK have provided drug-able targets and companion diagnostics in several diseases, yet many transforming events in humans are polygenic, complex and incompletely understood at a genomic level. Recognition that oncogenesis reflects changes in the cell and its micro environment has renewed interest in whole cell experimental models that capture native-state cell-cell, -stroma and -vascular signaling. Ex vivo analysis of programmed cell death (EVA/PCD) has been shown to correlate significantly with response, time to progression and survival (Nagourney, R. Curr. Treat Op Oncol, 2006).To explore EVA/PCD functional profiling in Brazil, hospital-based investigators, Centro de Genomas and Rational Therapeutics coordinated the transport of 67 surgical specimens for analyses.
Methods:
Dose-response curves using metabolic (ATP-content, mitochondrial) and morphologic endpoints, interpolated to LC50's and synergy by median-effect, were compared with databases to identify patient-specific profiles for cytotoxics, targeted agents and combinations. Reports provided day 7.
Results:
62/67 (92%) provided adequate tumor for analysis; 39 male (58%); 28 (42%) female; 6 chemo-naive and 61 previously treated. Results provided for < 8 drugs in 14/62 (22%); 8-16 drugs in 34/62 (54%) and > 16 drugs in 14/62 (22%). Of 22 tumor types, breast (8); Melanoma (8); NSCLC (8); ovary (7); pancreas (7) and sarcoma (4) predominated. EVA/PCD was used to select the most active combinations. Agents selected, response rates and durations are being tabulated and will be reported.
Conclusions:
The transport, processing and reporting of human tumor primary culture analyses is feasible, providing results in 92% of specimens and median of 12 drugs evaluated (range 4-32). Preliminary outcomes in these drug-refractory patients reveal that novel, often unexpected drug combinations (Everolimus and Lapatinib in triple negative breast) were identified and provided objective tumor responses, supporting EVA/PCD in therapy selection (personalized therapy) and drug development.
http://meetinglibrary.asco.org/content/117655-132