Later, increasing evidence has demonstrated that other concomitant alterations such as mutations or amplification also accelerated the resistance to TKIs (13, 14)
November 26, 2021
Later, increasing evidence has demonstrated that other concomitant alterations such as mutations or amplification also accelerated the resistance to TKIs (13, 14). of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with mutations and other potentially actionable drivers such as amplification (21.6%; 8/37) and alterations in including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in were also identified. Additionally, amplification in patients harboring tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes. Conclusions Approximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies. mutations, rearrangements, rearrangements, V600E mutation, rearrangements, and rearrangements (2C4). The targeted therapies for alterations (exon 14 splicing site mutations also known as skipping mutations or amplification), alterations (mutations or amplification), and G12C mutation Ctsl also demonstrated promising efficacies in clinical trials, paving a way for precision medicine of NSCLC (4C8). More and more targeted drugs were put into the first-line setting, greatly influencing the treatment strategies; however, even with the same type of actionable drivers, the efficacy of targeted therapies varies from patient to patient (9). Several studies have proved that both progression-free survival (PFS) and overall survival (OS) of mutant or rearranged NSCLCs with mutations receiving or TKIs, respectively, were significantly lower than those of patients without mutations (10C12). Later, increasing evidence has demonstrated that other concomitant alterations such as mutations or amplification also accelerated the resistance to TKIs (13, 14). In addition to these common co-existing mutations without available targeted drugs, co-occurring targetable oncogenic drivers can also be found in a small number of NSCLCs (15C18); however, there is still little evidence to make precision treatment plans for these patients, whose demographic and KIN-1148 clinical characteristics remained KIN-1148 largely unknown. Based on a large population who underwent next-generation sequencing (NGS) in Shanghai Chest Hospital, our study revealed the characteristics and prognosis of NSCLC patients with co-occurring potentially actionable oncogenic drivers, trying to optimize the treatment strategies. Patients and Methods Patients Between March 2018 and June 2019, patients with NSCLC analyzed for possible actionable targets by NGS in Shanghai Chest Hospital were enrolled. All patients were diagnosed as adenocarcinoma, squamous cell carcinoma, and other NSCLCs according to World Health Organization criteria assessed by experienced pathologists. The baseline clinical and demographic characteristics including age, gender, pathology, and stage were retrospectively collected. Our study has been approved by the institutional review board of Shanghai Chest Hospital. Written consent forms were obtained from patients before all invasive procedures and initiation of tyrosine kinase inhibitors (TKIs). Next-Generation Sequencing NGS is routinely carried out for patients with advanced NSCLCs, especially adenocarcinomas, in our center unless they refuse to do so. Patients with early stage NSCLCs can also choose to receive NGS in case of recurrence. A total of 3,077 formalin-fixed, paraffin-embedded (FFPE) tumor samples acquired from resected lung or small biopsies from NSCLCs were prepared according to standard procedure. Samples with more than 5% tumor content were sent for NGS. Tissue DNA was extracted KIN-1148 by QIAamp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany) and then evaluated with the Qubit 3.0 dsDNA assay (Life Technologies, CA, USA). DNA was fragmented by the Covaris M220 Focused-Ultrasonicator (Covaris, Woburn, MA), followed by end repair, phosphorylation, and adaptor.