Un estudio retrospectivo de Manuel Hidalgo y cols. (“Potencial use of pharmacogenomic modelling for patients stratification in the Phase II trial of PM01183 in pancreatic cancer”) destaca la utilidad de los tests genómicos para lograr una mejor estratificación de los pacientes con cáncer de páncreas que son candidatos a tratamiento con el antitumoral PM01183.
En concreto, se han empleado estos tests para evaluar perfiles de quimiosensibilidad, con el objetivo de predecir qué pacientes son susceptibles de ser incluidos en un estudio fase II con PM01183 e, incluso, para predecir la tasa de respuesta.
En este estudio retrospectivo sobre 32 pacientes, los autores concluyeron que 3 pacientes tuvieron un perfil de quimiosensibilidad positivo a PM01183, 2 de los cuales podían presentar una respuesta clínica al PM01183, que fue demostrada finalmente en uno de ellos.
De esta forma, se reafirma la hipótesis de que estas técnicas de evaluación de la quimiosensibilidad podrían ser útiles, en el futuro, para mejorar la selección de los pacientes que pudieran participar en los ensayos clínicos de este fármaco.
*********************************************
Presentation Time: Wednesday, Apr 09, 2014, 8:00 AM -12:00 PM
Author Block:
Manuel Hidalgo, Mark Ricigliano, Brandon Cooper, Miguel Aracil Avilla, Carlos Galmarini.Spanish National Cancer Ctr. (CNIO), Madrid, Spain; CellPath Therapeutics, Inc, Rockville, MD; PharmaMar, Madrid, Spain
Abstract Body:
Background:
Pharmacogenomic assays (PGx) can be effectively used to enrich a patient population for a clinical trial. Only those patients predicted to respond a priori to a chemotherapeutic either as a single-agent or in combination should be enrolled. Critical data obtained from patient stratification based on chemosensitivity profiles can be used to further develop companion diagnostics and inform future drug development strategy.
The objective of this retrospective study was to evaluate if chemosensitivity profiles could have been used to predict the enrollment status and overall response rate of 32 study participants in the Phase II trial of PM01183 in pancreatic cancer. Methods.
Patients with pancreatic adenocarcinoma who progressed following 1st line gemcitabine treatment were enrolled and venous blood was collected in a standard 10 ml sodium heparin Vacutainer tube. Circulating tumor and invasive cells (CTIC) were isolated using a modified cell invasion assay (Vitatex, Stony Brook, NY), and RNA from the isolated CTICs was extracted for microarray gene-expression analysis (Affymetrix, Santa Clara CA). Tumor growth inhibition data from 24 cancer cell lines was obtained and was used to construct the PGx model of PM01183.
Chemosensitivity profiles for each patient based on 10 chemotherapeutics was determined using proprietary software (CellPath Therapeutics, Inc. Baltimore, MD). Non-parametric rank correlation was then used to obtain an R-value of the patient sensitivity profile compared to the PM01183 template to determine enrollment status. Only patients with a positive correlated chemosensitivity profile (R+) to the PM01183 template should have been enrolled in the study.
Results:
Three patients (9%) presented a sensitivity profile that was R+ to the PM01183 template and would have been enrolled if the chemosensitivity profile assay were used prospectively. Of the three patients selected, only two patients presented an R-value > 0.20 which would have indicated a potential clinical response to PM01183. Of the two patients selected as potential responders, one patient clinically demonstrated a PR.
Conclusion :
The chemosensitivity profile assay for PM01183 correctly identified the one PR in the 32 patients cohort. These data warrant further efforts to confirm the potential of the chemosensitivity profile in a larger series of patients and disease types. If confirmed, this technique could be useful to guide patient recruitment in clinical trials.
FDA разрешило испанской компании PharmaMar, подразделению Grupo Zeltia, начать производство препарата PM1183, предназначенного для лечения рака груди и других видов опухолей.
