Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients from a phase 1 study of rociletinib (CO-1686)
A partir d'échantillons sanguins prélevés sur un total de 174 patients atteints d'un cancer du poumon non à petites cellules, cette étude évalue l'intérêt d'analyser l'ADN tumoral circulant pour détecter l'apparition de la mutation T790M du gène EGFR conférant une résistance aux inhibiteurs d'EGFR de première génération
Purpose: The evaluation of plasma testing for the EGFR resistance mutation T790M in NSCLC patients has not been broadly explored. We investigated the detection of EGFR activating and T790M mutations in matched tumor tissue and plasma, mostly from patients with acquired resistance to first-generation EGFR inhibitors.
Experimental Design: Samples were obtained from 2 studies, an observational study and a phase 1 trial of rociletinib, a mutant-selective inhibitor of EGFR that targets both activating mutations and T790M. Plasma testing was performed with the cobas® EGFR plasma test and BEAMing.
Results: The positive percent agreement (PPA) between cobas® plasma and tumor results was 73% (55/75) for activating mutations and 64% (21/33) for T790M. The PPA between BEAMing plasma and tumor results was 82% (49/60) for activating mutations and 73% (33/45) for T790M. Presence of extrathoracic (M1b) vs. intrathoracic (M1a/M0) disease was found to be strongly associated with ability to identify EGFR mutations in plasma (p < 0.001). Rociletinib objective response rates (ORR) were 67% (95% CI, 47-87%) for cobas® tumor T790M-positive and 56% (95% CI, 37-75%) for BEAMing plasma T790M-positive patients. A drop in plasma mutant EGFR levels to ≤10 molecules/mL was seen by Day 21 of treatment in 7 of 8 patients with documented partial response.
Conclusions: These findings suggest the cobas® and BEAMing plasma tests can be useful tools for non-invasive assessment and monitoring of the T790M resistance mutation in NSCLC, and could complement tumor testing by identifying T790M mutations missed because of tumor heterogeneity or biopsy inadequacy.
Clinical Cancer Research , article en libre accès, 2016