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)
BackgroundThe use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.MethodsWe 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.874712/full |
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| author | Ari Raphael Ari Raphael Amir Onn Amir Onn Liran Holtzman Julia Dudnik Damien Urban Waleed Kian Aharon Y. Cohen Mor Moskovitz Alona Zer Jair Bar Jair Bar Natalie Maimon Rabinovich Shirly Grynberg Cecilie Oedegaard Abed Agbarya Nir Peled Nir Peled Tzippy Shochat Elizabeth Dudnik Elizabeth Dudnik Elizabeth Dudnik |
| author_facet | Ari Raphael Ari Raphael Amir Onn Amir Onn Liran Holtzman Julia Dudnik Damien Urban Waleed Kian Aharon Y. Cohen Mor Moskovitz Alona Zer Jair Bar Jair Bar Natalie Maimon Rabinovich Shirly Grynberg Cecilie Oedegaard Abed Agbarya Nir Peled Nir Peled Tzippy Shochat Elizabeth Dudnik Elizabeth Dudnik Elizabeth Dudnik |
| author_sort | Ari Raphael |
| collection | DOAJ |
| description | BackgroundThe use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.MethodsWe 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.ResultsIn 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).ConclusionCGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2nd/3rd-generation ALK TKIs. |
| first_indexed | 2024-12-12T03:31:53Z |
| format | Article |
| id | doaj.art-f85c5c5f27684af1b3b0753d584f245f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T03:31:53Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f85c5c5f27684af1b3b0753d584f245f2022-12-22T00:39:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.874712874712The 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)Ari Raphael0Ari Raphael1Amir Onn2Amir Onn3Liran Holtzman4Julia Dudnik5Damien Urban6Waleed Kian7Aharon Y. Cohen8Mor Moskovitz9Alona Zer10Jair Bar11Jair Bar12Natalie Maimon Rabinovich13Shirly Grynberg14Cecilie Oedegaard15Abed Agbarya16Nir Peled17Nir Peled18Tzippy Shochat19Elizabeth Dudnik20Elizabeth Dudnik21Elizabeth Dudnik22Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelThoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelThoracic Oncology Service, Cancer Institute, Soroka University Medical Center, Beer-Sheva, IsraelThoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, IsraelDepartment of Oncology, Shaare Zedek Medical Center, Jerusalem, IsraelThoracic Oncology Service, Cancer Institute, Soroka University Medical Center, Beer-Sheva, IsraelThoracic Cancer Service, Rambam Health Care Campus, Haifa, IsraelThoracic Cancer Service, Rambam Health Care Campus, Haifa, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelThoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, IsraelThoracic Cancer Service, Meir Medical Center, Kfar Sava, IsraelThoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, IsraelThoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, IsraelDepartment of Oncology, Bnai Zion Medical Center, Haifa, IsraelDepartment of Oncology, Shaare Zedek Medical Center, Jerusalem, IsraelFaculty of Health Sciences, Ben Gurion University of Negev, Beer-Sheva, Israel0Statistical Consulting Unit, Rabin Medical Center, Petah Tikva, IsraelFaculty of Health Sciences, Ben Gurion University of Negev, Beer-Sheva, Israel1Thoracic Oncology Service, Assuta Medical Centers, Tel-Aviv, Israel2Thoracic Oncology Service, Rabin Medical Center, Petah Tikva, IsraelBackgroundThe use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.MethodsWe 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.ResultsIn 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).ConclusionCGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2nd/3rd-generation ALK TKIs.https://www.frontiersin.org/articles/10.3389/fonc.2022.874712/fullcomprehensive genomic profilingnext-generation sequencingALKfailure of ALK TKIacquired resistancedecision impact |
| spellingShingle | Ari Raphael Ari Raphael Amir Onn Amir Onn Liran Holtzman Julia Dudnik Damien Urban Waleed Kian Aharon Y. Cohen Mor Moskovitz Alona Zer Jair Bar Jair Bar Natalie Maimon Rabinovich Shirly Grynberg Cecilie Oedegaard Abed Agbarya Nir Peled Nir Peled Tzippy Shochat Elizabeth Dudnik Elizabeth Dudnik Elizabeth Dudnik 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) Frontiers in Oncology comprehensive genomic profiling next-generation sequencing ALK failure of ALK TKI acquired resistance decision impact |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | comprehensive genomic profiling next-generation sequencing ALK failure of ALK TKI acquired resistance decision impact |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.874712/full |
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