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Clinical Implications of Plasma-Based Genotyping with the Delivery of Personalized Therapy in Metastatic Non–Small Cell Lung Cancer

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Clinical Implications of Plasma-Based Genotyping with the Delivery of Personalized Therapy in Metastatic Non–Small Cell Lung Cancer Supplementary Online Content Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non–small cell lung cancer. JAMA Oncology. Published online October 11, 2018. doi:10.1001/jamaoncol.2018.4305 eTable 1. Plasma-based Circulating Tumor DNA and Tissue Next-Generation Sequencing Gene Panels eTable 2. Clinically Relevant and Therapeutically Targetable Mutations eTable 3. Liquid Biopsy–Detected Mutations for the 323 Patients Enrolled in the Study eTable 4. Patient Characteristics eTable 5. Forty-two Patients Who Received Targeted Therapy Indicated by Plasma eFigure 1. Analysis of Mutations Detected in Plasma and/or Tissue NGS eFigure 2. Correlation of Tissue AF for the Targeted Mutation and Depth of RECIST Response to Targeted Therapy in 10 Patients with Tissue and Plasma Available This supplementary material has been provided by the authors to give readers additional information about their work. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 1. Plasma-based Circulating Tumor DNA and Tissue Next-Generation Sequencing Gene Panels A. Guardant360 Panel (73 genes) SNVs AKT1 ALK APC AR ARAF ARID1A ATM BRAF BRCA1 BRCA2 CCDN1 CCDN2 CCNE1 CDH1 CDK4 CDK6 CDKN2A CTNNB1 DDR2 EGFR ERBB2 ESR1 EZH2 FBXW7 FGFR1 FGFR2 FGFR3 GATA3 GNA11 GNAQ GNAS HNF1A HRAS IDH1 IDH2 JAK2 JAK3 KIT KRAS MAP2K1 MAP2K2 MAPK1 MAPK3 MET MLH1 MPL MTOR MYC NF1 NFE2L2 NOTCH1 NPM1 NRAS NTRK1 NTRK3 PDGFRA PIK3CA PTEN PTPN11 RAF1 RB1 RET RHEB RHOA RIT1 ROS1 SMAD4 SMO STK11 TERT TP53 TSC1 VHL Indels ATM APC ARID1A BRCA1 BRCA2 CDH1 CDKN2A EGFR ERBB2 GATA3 KIT MET MLH1 MTOR NF1 PDGFRA PTEN RB1 SMAD4 STK11 TP53 TSC1 VHL Fusions ALK FGFR2 FGFR3 NTRK1 RET ROS1 B. Center for Personalized Diagnostics Panel v.2.0 (153 genes) –used as of 9/12/2016a ABL1 AKT1 AKT2 AKT3 ALK APC AR ARAF ARID1A ARID2 ATM ATRX AURKA BAP1 BRAF BRCA1 BRCA2 BRIP BTK CBP CCND1 CCND2 CCND3 CCNE1 CDH1 CDK4 CDK6 CDKN2A CHEK2 CIC CRKL CSF1R CTNNB1 DAXX DDR2 DNMT3A EGFR EIF1Ax EPHA3 ERBB2 ERBB3 ERBB4 ERCC2 ERG ESR1 ESR2 EZH2 FBXW7 FGF3 FGFR1 FGFR2 FGFR3 FGFR4 FLT3 FUBP1 GATA3 GNA11 GNAQ GNAS HRAS H3F3A IDH1 IDH2 IGF1R JAK1 JAK2 JAK3 KDM5A KDM5C KDM6A KDR KIT KMT2C KRAS MAP2K1 MAP2K2 MAP2K4 MAPK1 MAPK3 MAX MCL1 MDM2 MDM4 MED12 MEN1 MET MITF MLH1 MRE11A MSH2 MSH6 MTOR MYC MYCN NBN NF1 NF2 NTRK1 NTRK2 NTRK3 NKX2‐1 NOTCH1 NOTCH2 NOTCH3 NRAS EP300 PAK1 PALB2 PBRM1 PDGFRA PIK3CA PIKC3B PIK3R1 PTCH1 PTEN PTPN11 RAB35 RAC1 RAD50 RAD51 RAD51B RAD51C RAD51D RAF1 RB1 RET RHOA RNF43 SETD2 SF3B1 SLIT2 SMAD4 SMARCA4 SMO SPOP SRC STAG2 STK11 SUFU SUZ12 SYK TERT TET2 TGFBR2 TP53 TRAF7 TSC1 TSC2 TSHR U2AF1 VHL WT1 XRCC2 C. Penn Precision Panel (20 genes) AKT1 ALK BRAF CSF1R EGFR ERBB2 HRAS IDH1 IDH2 KIT KRAS MAP2K1 MET NOTCH1 NRAS PDGFRA PIK3CA PTEN RET TP53 aBolded: genes present in CPD Panel v.1.0 (47 genes) used prior to 9/12/2016. The following genes were present in CPD Panel v.1.0 but not v.2.0: HNF1A, MPL, NPM1, SMARCB1, STK. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 2. Clinically Relevant and Therapeutically Targetable Mutations © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eTable 3. Liquid Biopsy–Detected Mutations for the 323 Patients Enrolled in the Study Patient Histology Gene Variant MAF Clonality Clonality ID calculation 00001 N ALK‐EML4 Fusion 0.20 1.00 clonal 00001 N CTNNB1 S45P 0.10 0.50 clonal 00002 N TP53 I254T 0.80 1.00 clonal 00002 N TP53 P177H 0.20 0.25 clonal 00008 N PTPN11 Q510H 1.50 1.00 clonal 00008 N KRAS G12V 0.20 0.13 subclonal 00009 N EGFR Exon19del 37.20 1.00 clonal 00009 N EGFR T790M 29.90 0.80 clonal 00009 N TP53 C182* 23.40 0.63 clonal 00009 N AR E213K 6.10 0.16 subclonal 00009 N BRCA1 T164A 3.80 0.10 subclonal 00012 N KRAS G13C 2.50 1.00 clonal 00012 N EGFR G197G 0.80 0.32 clonal 00012 N MET P1171L 0.80 0.32 clonal 00012 N RB1 I103I 0.70 0.28 clonal 00012 N RB1 I101I 0.60 0.24 clonal 00012 N CDKN2B R105Q 0.20 0.08 subclonal 00014 N EGFR T790M 1.50 1.00 clonal 00014 N EGFR Exon19del 1.00 0.67 clonal 00021 N PIK3CA V850G 0.50 1.00 clonal 00021 N RET V650M 0.30 0.60 clonal 00022 N TP53 H179Y 3.70 1.00 clonal 00022 N RB1 K94* 0.90 0.24 clonal 00022 N PIK3CA E545K 0.90 0.24 clonal 00022 N TP53 R196* 0.70 0.19 subclonal 00022 N EGFR Exon19del 0.50 0.14 subclonal 00022 N FGFR1 G697G 0.30 0.08 subclonal 00026 N NF1 R897Q 0.40 1.00 clonal 00027 N RB1 E748* 16.50 1.00 clonal 00027 N EGFR L858R 13.00 0.79 clonal 00027 N TP53 R213* 8.90 0.54 clonal 00027 N PTEN Q17* 6.10 0.37 clonal 00027 N APC D2663V 1.60 0.10 subclonal 00027 N EGFR T790M 1.30 0.08 subclonal 00027 N NOTCH1 A1650A 0.20 0.01 subclonal 00027 N AR E213K 0.20 0.01 subclonal 00027 N FGFR2 L258L 0.20 0.01 subclonal 00027 N NF1 L847P 0.20 0.01 subclonal 00031 N EGFR E709A 4.90 1.00 clonal 00031 N EGFR G719A 4.80 0.98 clonal 00031 N CTNNB1 S37F 1.00 0.20 clonal 00031 N NOTCH1 Q2416P 0.30 0.06 subclonal 00031 N ARID1A Q520P 0.30 0.06 subclonal 00031 N TP53 R248Q 0.2 0.04 subclonal © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 00031 N TP53 M246L 0.2 0.04 subclonal 00031 N TP53 R65fs 0.05 0.01 subclonal 00033 N TP53 Y220* 32.30 1.00 clonal 00033 N TP53 H193R 0.20 0.01 subclonal 00034 N TP53 N210K 9.90 1.00 clonal 00034 N TP53 F212F 9.90 1.00 clonal 00034 N TP53 T211I 9.80 0.99 clonal 00034 N EGFR L858R 9.60 0.97 clonal 00034 N MET E1390K 2.70 0.27 clonal 00034 N TP53 R273C 0.30 0.03 subclonal 00034 N TP53 C275Y 0.20 0.02 subclonal 00034 N BRAF D118D 0.20 0.02 subclonal 00034 N NTRK1 T470K 0.20 0.02 subclonal 00034 N HNF1A R263C 0.20 0.02 subclonal 00034 N NF1 R2450* 0.10 0.01 subclonal 00035 N TP53 G262V 5.60 1.00 clonal 00035 N KRAS G12D 2.80 0.50 clonal 00036 N ERBB2 Q178Q 1.00 1.00 clonal 00036 N AR A403V 0.20 0.20 clonal 00036 N EGFR L858R 0.10 0.10 subclonal 00038 N EGFR Exon19del 4.90 1.00 clonal 00038 N TP53 Q136* 1.90 0.39 clonal 00038 N EGFR T790M 1.60 0.33 clonal 00038 N NF1 M1409T 1.10 0.22 clonal 00038 N ERBB2 R351* 0.10 0.02 subclonal 00041 N N/A WT Report WT Report 00042 N TERT L38L 0.60 1.00 clonal 00043 N RB1 C278S 0.70 1.00 clonal 00043 N EGFR Exon19del 0.20 0.29 clonal 00043 N EGFR T790M 0.20 0.29 clonal 00043 N EGFR P644P 0.10 0.14 subclonal 00044 N ROS1 A1832T 2.60 1.00 clonal 00044 N TP53 R248Q 2.50 0.96 clonal 00044 N NF1 T2741T 0.20 0.08 subclonal 00044 N ARID1A D2229N 0.10 0.04 subclonal 00046 N TP53 P278A 1.80 1.00 clonal 00046 N TP53 R249S 1.40 0.78 clonal 00046 N TP53 R158L 0.30 0.17 subclonal 00046 N MET T67T 0.30 0.17 subclonal 00047 N CDKN2A S12L 0.50 1.00 clonal 00047 N KRAS G12C 0.40 0.80 clonal 00047 N PDGFRA R376Q 0.10 0.20 clonal 00050 N N/A WT Report WT Report 00051 N JAK2 V617F 0.60 1.00 clonal 00051 N ATM V3032E 0.40 0.67 clonal 00053 N ALK R1120W 0.10 1.00 clonal 00054 N N/A WT Report WT Report 00056 N PDGFRA D154N 0.20 1.00 clonal © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 00057 N EGFR L858R 6.50 1.00 clonal 00057 N TP53 Q144P 2.30 0.35 clonal 00057 N AR R841G 2.00 0.31 clonal 00057 N CCND1 M113I 0.10 0.02 subclonal 00059 N TP53 Y163C 2.80 1.00 clonal 00059 N EGFR Exon19del 2.20 0.79 clonal 00059 N CDKN2A P48L 2.20 0.79 clonal 00060 N APC R2505Q 0.20 1.00 clonal 00060 N AR M750V 0.20 1.00 clonal 00067 N TP53 R273H 0.50 1.00 clonal 00067 N PIK3CA G106V 0.50 1.00 clonal 00068 N STK11 K44* 4.70 1.00 clonal 00068 N FGFR1 T82T 2.90 0.62 clonal 00069 N N/A WT Report WT Report 00074 N DDR2 R806* 0.40 1.00 clonal 00074 N EGFR Exon19del 0.20 0.50 clonal 00076 N ALK‐EML4 Fusion 0.10 1.00 clonal 00076 N EML4‐ALK Fusion 0.10 1.00 clonal 00077 S GNAS R201H 17.00 1.00 clonal 00077 S TP53 D259Y 14.10 0.83 clonal 00077 S CDKN2A D84Y 4.20 0.25 clonal 00077 S ARID1A T238P 0.70 0.04 subclonal 00077 S ERBB2 C584G 0.40 0.02 subclonal 00077 S TERT L681R 0.30 0.02 subclonal 00077 S ERBB2 V697G 0.20 0.01 subclonal 00078 N N/A WT Report WT Report 00081 N NF1 Exon32del 3.30 1.00 clonal 00081 N EGFR L858R 2.40 0.73 clonal 00081 N MET V854I 0.30 0.09 subclonal 00081 N MET R191Q 0.10 0.03 subclonal 00083 N EGFR L858R 21.10 1.00 clonal 00083 N EGFR T790M 4.70 0.22 clonal 00084 N N/A WT Report WT Report 00085 S ALK I1171I 0.90 1.00 clonal 00085 S GNAS R201C 0.90 1.00 clonal 00085 S ARID1A Q507* 0.70 0.78 clonal 00085 S NRAS G12A 0.60 0.67 clonal 00085 S MET E924K 0.30 0.33 clonal 00086 N TP53 H179Q 0.10 1.00 clonal 00087 N EGFR Exon19del 6.90 1.00 clonal 00087 N TP53 R273C 3.10 0.45 clonal 00087 N KIT G663R 1.20 0.17 subclonal 00087 N ARID1A R1656R 0.40 0.06 subclonal 00087 N EGFR L12R 0.30 0.04 subclonal 00087 N ERBB2 V314I 0.10 0.01 subclonal 00087 N FGFR2 K505* 0.10 0.01 subclonal 00089 N NF1 E1787* 6.80 1.00 clonal 00089 N TP53 Y205C 0.20 0.03 subclonal © 2018 American Medical Association.
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