The Impact of Comprehensive Genomic Profiling (CGP) on the Decision-Making Process in the Treatment of ALK-Rearranged Advanced Non-Small Cell Lung Cancer (aNSCLC) After Failure of 2nd/3rd-Generation ALK Tyrosine Kinase Inhibitors (TKIs)
Copyright © 2022 Raphael, Onn, Holtzman, Dudnik, Urban, Kian, Cohen, Moskovitz, Zer, Bar, Rabinovich, Grynberg, Oedegaard, Agbarya, Peled, Shochat and Dudnik..
Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.
Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2nd/3rd-generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT). Patients were divided into groups: patients in whom the NLST was initiated after (group 1) and before (group 2) receival of the CGP results. Time-to-treatment discontinuation (TTD) and overall survival (OS) with NLST were compared between the groups.
Results: In 20 eligible patients (median [m]age 63 years [range, 40-89], females 75%, adenocarcinoma 100%, failure of alectinib 90%, FoundationOne Liquid CDx 80%), CGP has altered NLST recommendation in 30% of cases. CGP findings were as follows: ALK mutations 30% (l1171X 10%, G1202R, L1196M, G1269A, G1202R+l1171N+E1210K 5% each), CDKN2A/B mutation/loss 10%, c-met amplification 5%. CGP mTAT was 2.9 weeks [IQR, 2.4-4.4]. mTTD was 11.3 months (95% CI, 2.1-not reached [NR]) and 5.4 months (95% CI, 2.0-NR) in groups 1 and 2, respectively (p-0.34). mOS was 13.2 months (95% CI, 2.9-NR) and 13.0 months (95% CI, 6.0-NR) in groups 1 and 2, respectively (p-0.86).
Conclusion: CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2nd/3rd-generation ALK TKIs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Frontiers in oncology - 12(2022) vom: 23., Seite 874712 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Raphael, Ari [VerfasserIn] |
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| Links: |
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| Themen: |
ALK |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2022.874712 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Raphael, Ari |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Impact of Comprehensive Genomic Profiling (CGP) on the Decision-Making Process in the Treatment of ALK-Rearranged Advanced Non-Small Cell Lung Cancer (aNSCLC) After Failure of 2nd/3rd-Generation ALK Tyrosine Kinase Inhibitors (TKIs) |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2022 Raphael, Onn, Holtzman, Dudnik, Urban, Kian, Cohen, Moskovitz, Zer, Bar, Rabinovich, Grynberg, Oedegaard, Agbarya, Peled, Shochat and Dudnik. | ||
| 520 | |a Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable | ||
| 520 | |a Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2nd/3rd-generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT). Patients were divided into groups: patients in whom the NLST was initiated after (group 1) and before (group 2) receival of the CGP results. Time-to-treatment discontinuation (TTD) and overall survival (OS) with NLST were compared between the groups | ||
| 520 | |a Results: In 20 eligible patients (median [m]age 63 years [range, 40-89], females 75%, adenocarcinoma 100%, failure of alectinib 90%, FoundationOne Liquid CDx 80%), CGP has altered NLST recommendation in 30% of cases. CGP findings were as follows: ALK mutations 30% (l1171X 10%, G1202R, L1196M, G1269A, G1202R+l1171N+E1210K 5% each), CDKN2A/B mutation/loss 10%, c-met amplification 5%. CGP mTAT was 2.9 weeks [IQR, 2.4-4.4]. mTTD was 11.3 months (95% CI, 2.1-not reached [NR]) and 5.4 months (95% CI, 2.0-NR) in groups 1 and 2, respectively (p-0.34). mOS was 13.2 months (95% CI, 2.9-NR) and 13.0 months (95% CI, 6.0-NR) in groups 1 and 2, respectively (p-0.86) | ||
| 520 | |a Conclusion: CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2nd/3rd-generation ALK TKIs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ALK | |
| 650 | 4 | |a acquired resistance | |
| 650 | 4 | |a comprehensive genomic profiling | |
| 650 | 4 | |a decision impact | |
| 650 | 4 | |a failure of ALK TKI | |
| 650 | 4 | |a next-generation sequencing | |
| 700 | 1 | |a Onn, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Holtzman, Liran |e verfasserin |4 aut | |
| 700 | 1 | |a Dudnik, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Urban, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Kian, Waleed |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Aharon Y |e verfasserin |4 aut | |
| 700 | 1 | |a Moskovitz, Mor |e verfasserin |4 aut | |
| 700 | 1 | |a Zer, Alona |e verfasserin |4 aut | |
| 700 | 1 | |a Bar, Jair |e verfasserin |4 aut | |
| 700 | 1 | |a Rabinovich, Natalie Maimon |e verfasserin |4 aut | |
| 700 | 1 | |a Grynberg, Shirly |e verfasserin |4 aut | |
| 700 | 1 | |a Oedegaard, Cecilie |e verfasserin |4 aut | |
| 700 | 1 | |a Agbarya, Abed |e verfasserin |4 aut | |
| 700 | 1 | |a Peled, Nir |e verfasserin |4 aut | |
| 700 | 1 | |a Shochat, Tzippy |e verfasserin |4 aut | |
| 700 | 1 | |a Dudnik, Elizabeth |e verfasserin |4 aut | |
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