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)

• Published in: Frontiers in oncology 2022, Vol.12, p.874712
• Main Authors: Raphael, 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
• Format: Article
• Language: English
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2022.874712

The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable. We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2 /3 -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. 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). CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2 /3 -generation ALK TKIs.