P89.13 Real-World Experience of NGS-Based Molecular Profiling in ‘Triple-Negative’ (EGFR/ALK/ROS1) Advanced NSCLC: Should we keep Testing Smokers?

Although promising, the impact of upfront multi-gene profiling in advanced non-small-cell lung cancer (aNSCLC) patients is not yet well defined in a real-world context of a general community hospital. From July 2018 to July 2020, next-generation sequencing (NGS) analyses were conducted on “triple negative” (EGFR/ALK/ROS1) aNSCLC patients diagnosed at San Bortolo General Hospital of Vicenza, Italy. The analyses were conducted on Formalin-Fixed Paraffin-Embedded (FFPE) tumor blocks and liquid biopsies in a multicenter compassionate program using Foundation One Medicine platform or Guardant 360 test. The aim of our analysis was to investigate the presence of potential druggable alterations and their correlation with baseline clinical factors. Overall, 46 aNSCLC patients were gathered. Median age was 64 years with 52% of male. Never smokers were 18 patients (39%) versus 28 former/current smokers (61%). 95% had an ECOG Performance Status of 0-1. 74% were metastatic at diagnosis with 88% of adenocarcinoma, 6% of squamous carcinoma and 6% not otherwise specified cancers. Complete molecular results were available in 36 patients (78%), as test failed in 10 patients (22%) due to insufficient material (tissue for 9 patients and liquid biopsy for 1 patient). Among 36 patients with available results, a druggable alteration was detected in 6 patients (17%). Among these, we found 1 EML4/ALK fusion (local ICH test was negative), 1 KIF5B-RET fusion, 1 BRAFV600E mutation, 2 MET exon 14 skipping alterations, 1 EGFR exon 18 E709_T710>D mutation. For all these patients an appropriate targeted treatment was started. No druggable alterations were found in smoker patients, as all these alterations were found in non-smoker patients in which molecular test was available (6/15). Smoking habit significantly predicted the absence of druggable alterations (p=0.009). Among therapeutically actionable alterations suitable for genome-driven clinical trials, KRAS G12C was found in 11% (4/36), ERBB2 alterations (A730T and P780–Y781insGSP) in 8% (3/36) and FGFR family alterations in 5% (2/36). These potentially druggable alterations were found in both former/current (6/21) and never-smoker patients (1/15). Our analysis suggests that NGS analyses may provide useful results in aNSCLC patients. Since clinically significant results were obtained only in non-smoker patients, we suggest smoking status as a potential clinical driver for selecting aNSCLC patients for NGS analyses in a real-world context. NGS testing of smokers might be considered within the research setting.