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Front Oncol

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 2(nd)/3(rd)-Generation ALK Tyrosine Kinase Inhibitors (TKIs)
Author(s):		Raphael A; Onn A; Holtzman L; Dudnik J; Urban D; Kian W; Cohen AY; Moskovitz M; Zer A; Bar J; Rabinovich NM; Grynberg S; Oedegaard C; Agbarya A; Peled N; Shochat T; Dudnik E;
Address:		"Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Thoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel. Thoracic Oncology Service, Cancer Institute, Soroka University Medical Center, Beer-Sheva, Israel. Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel. Thoracic Cancer Service, Rambam Health Care Campus, Haifa, Israel. Thoracic Cancer Service, Meir Medical Center, Kfar Sava, Israel. Department of Oncology, Bnai Zion Medical Center, Haifa, Israel. Faculty of Health Sciences, Ben Gurion University of Negev, Beer-Sheva, Israel. Statistical Consulting Unit, Rabin Medical Center, Petah Tikva, Israel. Thoracic Oncology Service, Assuta Medical Centers, Tel-Aviv, Israel. Thoracic Oncology Service, Rabin Medical Center, Petah Tikva, Israel"
Journal Title:		Front Oncol
Year:		2022
Volume:		20220513
Issue:
Page Number:		874712 -
DOI:		10.3389/fonc.2022.874712
ISSN/ISBN:		2234-943X (Print) 2234-943X (Electronic) 2234-943X (Linking)
Abstract:		"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 2(nd)/3(rd)-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 2(nd)/3(rd)-generation ALK TKIs"
Keywords:		Alk acquired resistance comprehensive genomic profiling decision impact failure of ALK TKI next-generation sequencing;
Notes:		"PubMed-not-MEDLINERaphael, Ari Onn, Amir Holtzman, Liran Dudnik, Julia Urban, Damien Kian, Waleed Cohen, Aharon Y Moskovitz, Mor Zer, Alona Bar, Jair Rabinovich, Natalie Maimon Grynberg, Shirly Oedegaard, Cecilie Agbarya, Abed Peled, Nir Shochat, Tzippy Dudnik, Elizabeth eng Switzerland 2022/06/02 Front Oncol. 2022 May 13; 12:874712. doi: 10.3389/fonc.2022.874712. eCollection 2022"