Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.

Introduction: Patients with lung cancer have a high prevalence of chronic obstructive pulmonary disease (COPD). There is a lack in our understanding of pathogenesis and mechanisms accounting for large variability in COPD phenotype. Airway dysbiosis have been implicated with disease severity and exacerbations in COPD. However, the role of gastrointestinal (GI) microbiome in pathogenesis of COPD has not been explored. Recent data suggest that the gut-lung axis regulates systemic immune function. Here, we aimed to evaluate the associations of GI microbiota and CAT score in lung cancer patients with COPD. Methods: We included stool samples from 98 lung cancer patients (adenocarcinoma (n=48), squamous cell (n=24), small cell lung cancer (n=15) and other (n=11). Of these, 59 had COPD and 39 did not have COPD. We analyzed the gut microbiome according to CAT score, FEV1, and chemotherapy (CHT) response using shotgun metagenomic sequencing technique. We performed Spearman correlation between gut microbial species and continuous variables. Results: Lachnospiraceae bacterium has a positive correlation (r=0.45) with CAT score. Non-responders had significantly higher CAT score (vs. responders, median CAT score of 23 vs 13, respectively (p<0.05). Correlation analysis for gut microbiome and CHT response and how FEV1 relates to the continuous variables will be presented at the conference. Conclusion: There were associations with certain gut bacteria species and CAT score. Higher CAT score associates with non-response to CHT administered to lung cancer patients.