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Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686).
Karlovich, Chris; Goldman, Jonathan W; Sun, Jong-Mu; Mann, Elaina; Sequist, Lecia V; Konopa, Krzysztof; Wen, Wei; Angenendt, Philipp; Horn, Leora; Spigel, David; Soria, Jean-Charles; Solomon, Benjamin; Camidge, D Ross; Gadgeel, Shirish; Paweletz, Cloud; Wu, Lin; Chien, Sean; O'Donnell, Patrick; Matheny, Shannon; Despain, Darrin; Rolfe, Lindsey; Raponi, Mitch; Allen, Andrew R; Park, Keunchil; Wakelee, Heather.
Afiliación
  • Karlovich C; Clovis Oncology Inc., San Francisco, California.
  • Goldman JW; University of California Los Angeles, Los Angeles, California. JWGoldman@mednet.ucla.edu hwakelee@stanford.edu.
  • Sun JM; Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Mann E; Clovis Oncology Inc., San Francisco, California.
  • Sequist LV; Massachusetts General Hospital, Boston, Massachusetts.
  • Konopa K; Medical University of Gdansk, Gdansk, Poland.
  • Wen W; Roche Molecular Systems, Pleasanton, California.
  • Angenendt P; Sysmex Inostics GmbH, Hamburg, Germany.
  • Horn L; Vanderbilt University School of Medicine, Nashville, Tennessee.
  • Spigel D; Sarah Cannon Research Institute, Nashville; Tennessee.
  • Soria JC; Institut Gustave Roussy, Villejuif, France.
  • Solomon B; University of Melbourne, Melbourne, Australia.
  • Camidge DR; University of Colorado, Denver, Colorado.
  • Gadgeel S; Karmanos Cancer Institute/Wayne State University, Detroit, Michigan.
  • Paweletz C; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Wu L; Roche Molecular Systems, Pleasanton, California.
  • Chien S; Roche Molecular Systems, Pleasanton, California.
  • O'Donnell P; Roche Molecular Systems, Pleasanton, California.
  • Matheny S; Clovis Oncology Inc., San Francisco, California.
  • Despain D; Clovis Oncology Inc., San Francisco, California.
  • Rolfe L; Clovis Oncology Inc., San Francisco, California.
  • Raponi M; Clovis Oncology Inc., San Francisco, California.
  • Allen AR; Clovis Oncology Inc., San Francisco, California.
  • Park K; Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
  • Wakelee H; Stanford University, Stanford, California. JWGoldman@mednet.ucla.edu hwakelee@stanford.edu.
Clin Cancer Res ; 22(10): 2386-95, 2016 05 15.
Article en En | MEDLINE | ID: mdl-26747242
ABSTRACT

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 two studies, an observational study and a phase I 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) versus 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 52% [95% confidence interval (CI), 31 - 74%] for cobas tumor T790M-positive and 44% (95% CI, 25 - 63%) 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 noninvasive 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. Clin Cancer Res; 22(10); 2386-95. ©2016 AACR.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Receptores ErbB / Neoplasias Pulmonares / Mutación Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Receptores ErbB / Neoplasias Pulmonares / Mutación Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article