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Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure.
Saw, Stephanie P L; Tan, Gek San; Tan, Wei Chong; Tan, Aaron C; Lai, Gillianne G Y; Lim, Darren W T; Kanesvaran, Ravindran; Tan, Wan Ling; Tan, Sze Huey; Lim, Kiat Hon; Skanderup, Anders J; Tan, Daniel S W.
Afiliación
  • Saw SPL; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • Tan GS; Duke-NUS Medical School, National University of Singapore, Singapore.
  • Tan WC; Division of Pathology, Singapore General Hospital, Singapore.
  • Tan AC; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • Lai GGY; Duke-NUS Medical School, National University of Singapore, Singapore.
  • Lim DWT; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • Kanesvaran R; Duke-NUS Medical School, National University of Singapore, Singapore.
  • Tan WL; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • Tan SH; Duke-NUS Medical School, National University of Singapore, Singapore.
  • Lim KH; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • Skanderup AJ; Duke-NUS Medical School, National University of Singapore, Singapore.
  • Tan DSW; Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
JTO Clin Res Rep ; 4(12): 100599, 2023 Dec.
Article en En | MEDLINE | ID: mdl-38162173
ABSTRACT

Introduction:

To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations.

Methods:

Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated.

Results:

Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively (p = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS.At a median of 8 (range 3-24) weeks post-TKI initiation, clearance of pEGFR was achieved in 68% (13 of 19) and 71% (15 of 21) using ddPCR and NGS, respectively. Concordance between ddPCR and NGS was 79% (kappa = 0.513, p = 0.013). Clearance of pEGFR was associated with longer median TTF (not reached versus 6 months, p = 0.03) and median decrease in CEA levels by 70% from baseline.In another cohort of 124 patients, decrease in CEA levels by greater than 70% within 90 days of TKI initiation was associated with doubling of both TTF and overall survival.

Conclusions:

Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JTO Clin Res Rep Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JTO Clin Res Rep Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos