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Attend this session at the
2019 ASCO Annual Meeting!


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A

Dynamic monitoring of circulating tumor DNA next-generation gene sequencing as a predictive biomarker of response and progression-free survival after pembrolizumab monotherapy in patients with advanced NSCLC.

Sub-category:
Circulating Biomarkers

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3040

Poster Board Number:
Poster Session (Board #32)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3040)

Author(s): Charu Aggarwal, Jeffrey C. Thompson, Austin Chien, Katie Quinn, Martina Lefterova, Rebecca Nagy, Stephanie Yee, Christine Agnes Ciunci, Evan W. Alley, Joshua Bauml, Roger B. Cohen, Corey J. Langer, Erica L. Carpenter; University of Pennsylvania, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; University of Pennsylvania Health System, Philadelphia, PA; Guardant Health, Redwood City, CA; Guardant Health, Inc., Redwood City, CA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; University of Pennsylvania Abramson Cancer Center, Philadelphia, PA

Abstract Disclosures

Abstract:

Background: Circulating tumor DNA next generation sequencing (ctDNA NGS) is increasingly being used to detect mutations (MT) in patients (pts) with metastatic (m) NSCLC. Limited data exist on the correlation of baseline ctDNA NGS profile and serial ctDNA NGS monitoring to response to immunotherapy. Methods: We conducted a prospective study in pts with mNSCLC receiving pembrolizumab monotherapy. Plasma was collected at weeks 0 (T0), 9 (T1), and 18 (T2). ctDNA NGS was performed using a 73 gene panel. Number of MTs and variant allelic fraction (VAF) were determined at baseline, and serially; change in mean VAF was calculated between T1-T0, and T2-T0. Response rate (RR) was assessed using RECIST 1.1. Correlations were made for pt characteristics, RR, progression free survival (PFS), and overall survival (OS). Results: We analyzed 95 samples from 33 pts, 21 female, median age 69 (range 51-89 years), smokers (n = 29), adenocarcinoma (n = 23), 25 pts enrolled at initial diagnosis, majority had high PD-L1 ≥50% (n = 29, 88%). At T0, 32 pts had detectable MT, median number of MTs was 4 (range 0-21), (non-synonymous MT = 3), most common MT was TP53 (n = 21). Confirmed PR was 27% (n = 9), clinical benefit rate (SD+PR) was 64% (n = 21), and 2 pts were not evaluable for response. Smokers were more likely to have higher number of MT at T0 (4 vs. 1 p = 0.003); there was no correlation with smoking and overall RR (p = 0.17). RR was not related to number of MT at T0, p = 0.37. A decrease in ctDNA VAF was seen in 6/9 pts with PR (mean VAF change range -0.11 to -0.001); 2/5 pts with PD showed an increase in mean VAF while 3 showed decrease. At median follow up of 9.26 months (mos), median PFS and OS were 7.4 and 10.5 mos, respectively. Median PFS was longer for pts with a decrease in ctDNA VAF at both T1-T0 (8.9 vs. 5 mos, p = 0.02) and T2-T0 (9.1 vs. 5.5 mos, p = 0.006). OS and additional biomarker analyses including correlation of response to a 2mb ctDNA plasma-based NGS panel will be reported at the meeting. Conclusions: Our results demonstrate that it is feasible to serially monitor plasma NGS, decline in mean ctDNA VAF correlates with radiographic response and PFS on immunotherapy with pembrolizumab.

 
Other Abstracts in this Sub-Category:

 

1. Genome-wide cell-free DNA fragmentation profiling for early cancer detection.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3018 First Author: Alessandro Leal
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

2. Multimodality liquid biopsy for early monitoring and outcome prediction in first-line metastatic HER2-negative breast cancer: Final results of the prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG)— COMET study.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3019 First Author: Jean-Yves Pierga
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

3. Circulating androgen receptor (AR) gene amplification and resistance to 177Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of a phase II clinical trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3020 First Author: Ugo De Giorgi
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

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