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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.

The immune checkpoint inhibitors (ICIs) have transformed the standards of care in cancer treatment and has dramatically improved patient prognoses. As a result of the introduction of these novel treatments several types of adverse events related to ICIs (immune related adverse events ((irAEs)) have been observed and reported. In this case series we describe the clinical course of four patients, with unusual ICI induced toxicities. The first patient was a 59 year-old female who received chemo-immunotherapy (pembrolizumab) for stage 4- lung adenocarcinoma, and developed autonomic neuropathy (AN). The second and third patients were both 63 year-old males who also received chemo-immunotherapy (pembrolizumab) for stage 4-A lung adenocarcinoma. One of those patients developed palmoplantar keratoderma and one developed conjunctivitis, urethritis and arthritis (Reiter syndrome). The fourth patient was an 80 year-old male who received chemo-immunotherapy (pembrolizumab) for stage 3-A squamous cell carcinoma of the lung and developed myasthenia gravis.