Plasma Genotyping at the Time of Diagnostic Tissue Biopsy Decreases Time-to-Treatment in Patients With Advanced NSCLC-Results From a Prospective Pilot Study

Jeffrey C Thompson, Charu Aggarwal, Janeline Wong, Vivek Nimgaonkar, Wei-Ting Hwang, Michelle Andronov, David M Dibardino, Christoph T Hutchinson, Kevin C Ma, Anthony Lanfranco, Edmund Moon, Andrew R Haas, Aditi P Singh, Christine A Ciunci, Melina Marmarelis, Christopher D'Avella, Justine V Cohen, Joshua M Bauml, Roger B Cohen, Corey J Langer, Anil Vachani, Erica L Carpenter, Jeffrey C Thompson, Charu Aggarwal, Janeline Wong, Vivek Nimgaonkar, Wei-Ting Hwang, Michelle Andronov, David M Dibardino, Christoph T Hutchinson, Kevin C Ma, Anthony Lanfranco, Edmund Moon, Andrew R Haas, Aditi P Singh, Christine A Ciunci, Melina Marmarelis, Christopher D'Avella, Justine V Cohen, Joshua M Bauml, Roger B Cohen, Corey J Langer, Anil Vachani, Erica L Carpenter

Abstract

Introduction: The availability of targeted therapies has transformed the management of advanced NSCLC; however, most patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored.

Methods: We performed a prospective cohort study of patients with suspected advanced lung cancer on the basis of cross-sectional imaging results. Blood from the time of biopsy was sequenced using a commercially available 74-gene panel. The primary outcome measure was time to first-line systemic treatment compared with a retrospective cohort of consecutive patients with advanced NSCLC with reflex tissue NGS.

Results: We analyzed the NGS results from 110 patients with newly diagnosed advanced NSCLC: cohorts 1 and 2 included 55 patients each and were well balanced regarding baseline demographics. In cohort 1, plasma NGS identified therapeutically informative driver mutations in 32 patients (58%) (13 KRAS [five KRAS G12C], 13 EGFR, two ERRB2, two MET, one BRAF, one RET). The NGS results were available before the first oncology visit in 85% of cohort 1 versus 9% in cohort 2 (p < 0.0001), with more cohort 1 patients receiving a guideline-concordant treatment recommendation at this visit (74% versus 46%, p = 0.005). Time-to-treatment was significantly shorter in cohort 1 compared with cohort 2 (12 versus 20 d, p = 0.003), with a shorter time-to-treatment in patients with specific driver mutations (10 versus 19 d, p = 0.001).

Conclusions: Plasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with usual care.

Keywords: Circulating tumor DNA; Lung cancer; Lung cancer genomics; Multidisciplinary; Precision medicine.

© 2022 The Authors.

Figures

Figure 1
Figure 1
Cohort flowchart.
Figure 2
Figure 2
Plasma genotyping mutational profile. Plasma genotyping results revealing SNVs (green), INDELs (purple), fusions (magenta), and gene amplifications (red) detected in each gene for the 55 patients in cohort 1. Each row indicates a gene for which one or more patients had a mutation detected, with rows ordered from top to bottom on the basis of decreasing prevalence of mutations. Number of variants detected in each patient is represented by the height of the top gray bars. The row at the bottom indicates NSCLC histology with nonsquamous (blue) and squamous (gold) histologies. #, number; AMP, amplification; INDEL, insertion/deletion; SNV, single-nucleotide variant.
Figure 3
Figure 3
Impact of plasma NGS at time of biopsy on time-to-treatment. (A) Comparison of the total number of driver mutations detected in both cohorts. (B) Comparison of NGS results available at the first oncology visit between cohorts. Tissue results available depicted in gray and plasma NGS results depicted in blue. (C) Percentage of patients receiving a specific treatment recommendation at the first oncology visit. (D) Median time-to-time treatment between cohorts. CohortD depicts patients with a therapeutically informative driver mutation detected. NGS, next-generation sequencing.

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Source: PubMed

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