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Charu Aggarwal
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ES01 - Choosing Systemic Therapies After Chemoimmunotherapy in NSCLC (ID 147)
- Event: WCLC 2020
- Type: Educational Session
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 09:15 - 10:15, Scientific Program Auditorium
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ES01.03 - Systemic Therapy after Chemo IO in Small Cell Lung Cancer (ID 3941)
09:15 - 10:15 | Presenting Author(s): Charu Aggarwal
- Abstract
- Presentation
Abstract not provided
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MA08 - Advances in Biomarkers for Immune Checkpoint Blockade and Targeted Therapy in Non Small Cell Lung Carcinoma (ID 166)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA08.10 - LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis (ID 3146)
16:45 - 17:45 | Author(s): Charu Aggarwal
- Abstract
Introduction
The national LUNGMAP clinical trial is predicated on molecular screening enabling patient enrollment to biomarker-matched sub-studies for rapid evaluation of new precision medicine concepts in advanced NSCLC. To date, LUNGMAP has used a tissue-based Next-Generation Sequencing (NGS) approach for biomarker assessment. Given the utility of circulating tumor DNA (ctDNA) for biomarker identification, LUNGMAP investigators are evaluating the feasibility of plasma ctDNA as a screening approach.
Methods
Plasma samples for ctDNA testing were required for patients submitting fresh tissue biopsies for LUNGMAP screening. Tissue and plasma ctDNA were analyzed using the FoundationONE CDx and FoundationACT platforms at Foundation Medicine, Inc., respectively. Alterations detectable in both platforms were evaluated. Using tissue-detected driver alterations (referred to as drivers) as the gold standard, sensitivity was calculated as the proportion of patients with drivers also detected in ctDNA in addition to tissue, and specificity was calculated as the proportion of patients without drivers in ctDNA among those without drivers in tissue. Proportions and 95% exact confidence interval (CI) estimates were calculated.
Results
From January 2019 to June 2020, 129 patients had paired data and 54 (42%) had recognized oncogene drivers detected (EGFR [n=7], KRAS [n=37], MET [n=7], RET [n=2], BRAF [n=1], Table 1). Fifty-two patients had drivers detected in tissue; of these 43 were also observed in ctDNA, with 9 found in tissue only, for a ctDNA driver sensitivity of 83% (43/52, 95% CI: 74-93%). Of the 77 patients with no drivers in tissue, 2 drivers were detected in ctDNA (EGFR Ex20ins, MET amp) for a ctDNA specificity of 97% (75/77, 95% CI: 91-100%). For drivers, median variant allele frequency (VAF) in ctDNA was 2.22% (range: 0.13%-46.27%). For all single nucleotide variants (SNVs) and rearrangements detectable on both platforms, 386 variants were detected. Short variants (point mutations and small in/dels) showed the most fidelity, with 54% detected in both platforms (Table 1). Copy number alterations using an earlier platform version were least reproduced, with 8% identified by both.
Conclusion
In the LUNGMAP population, ctDNA (FoundationAct) had an 83% sensitivity and 97% specificity for NSCLC drivers detected in tissue. For non-driver alterations, additional variants were detected exclusively in plasma or tissue, likely reflecting differential sensitivity and/or non-shedding and tissue heterogeneity. These results, consistant with other recent studies, support the planned use of ctDNA for enrollment onto LUNGMAP sub-studies, with a positive finding meriting inclusion in study but a negative finding, considered inconclusive, requiring use of tissue results.
Table 1 N (%)
Total Alterations Detected
Number of Patients
................... In ctDNA ................
...................... In Tissue ................
Overall
In Tissue
Not in Tissue
Overall
In ctDNA
Not in ctDNA
Driver Alterations
54
54
45
43 (96%)
2 (4%)
52
43 (83%)
9 (17%)
Non-driver Alterations
439
75
294
169 (57%)
125 (43%)
314
169 (54%)
145 (46%)
Short Variants
316
273
158 (58%)
115 (42%)
201
158 (79%)
43 (21%)
Copy Number Alts
104
10
8 (80%)
2 (20%)
102
8 (8%)
94 (92%)
Rearrangements
19
11
3 (27%)
8 (73%)
11
3 (27%)
8 (73%)
Overall
493
129
339
212 (63%)
127 (37%)
366
212 (58%)
154 (42%)
Short Variants
365
314
198 (63%)
116 (37%)
249
198 (80%)
51 (20%)
Copy Number Alts
107
12
9 (75%)
3 (25%)
104
9 (9%)
95 (91%)
Rearrangements
21
13
5 (38%)
8 (62%)
13
5 (38%)
8 (62%)
TP53
150
128
77 (60%)
51 (40%)
99
77 (78%)
22 (22%)
