Abstract
Osimertinib contributes to the higher efficacy and few intestinal side effects in non-small cell lung cancer (NSCLC) patients with T790M mutation. Previous studies has reported that intestinal microbiota play important roles in drug efficacy and toxicity. However, we have known less about the changes of intestinal microbiota in response to osimertinib therapy. In this pilot study, we used longitudinal sampling with 6 weeks sampling collection intervals for about 1 year to model intestinal microbial changes based on the 16S rRNA genes sequencing in fecal samples from NSCLC patients in response to osimertinib therapy. The results showed that there was no significantly different on the intestinal microbial composition at the phylum, family, and genus level among NSCLC patients with different treatment cycles (P > 0.05). There were no significant differences in alpha diversity characterized by the richness, Shannon diversity, and phylogenetic diversity based on the Welch’s t-test among NSCLC patients in response to osimertinib therapy (P > 0.05). However, the dissimilarity test and principal coordination analysis showed a few differences among NSCLC patients. The intestinal microbial markers were changed in post-therapy (Sutterella, Peptoniphilus, and Anaeroglobus) compared to that in pre-therapy (Clostridium XIVa). Furthermore, the phylogenetic molecular ecological networks (MENs) were influenced by osimertinib therapy based on the module number, link number, and module taxa composition of the first six groups. Overall, it indicated that osimertinib therapy changed the intestinal microbiota to some extent, though not completely. In all, this pilot study provides an understanding of changes of intestinal microbiota from NSCLC patients in response to osimertinib therapy. No complete changes in intestinal microbiota seem to be closely linked with the few intestinal side effects and higher efficacy in response to osimertinib therapy.
Highlights
Lung cancer remains the leading cause of cancer-related deaths worldwide (Torre et al, 2016)
non-small cell lung cancer (NSCLC) patients and control subjects were matched for age, sex as well as body mass index (BMI) in this study (Table 1)
We found that there was significantly different in beta diversity between pre-therapy and post-therapy in NSCLC patients based on the dissimilar test (P < 0.05, Supplementary Table S5), suggesting that osimertinib therapy has made the intestinal microbial community composition changed from the whole (Zhuang et al, 2019)
Summary
Lung cancer remains the leading cause of cancer-related deaths worldwide (Torre et al, 2016). For a long time, platinumbased chemotherapy has represented the cornerstone for the first-line treatment of advanced NSCLC patients (Santarpia et al, 2017a), with several limitations, including a number of side effects and a dismal overall survival. The development of specific molecularly targeted agents has primarily changed the therapeutic landscape for advanced NSCLC patients, including epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)-, anaplastic lymphoma kinase (ALK)-, and BRAF-inhibitors (Rosell and Karachaliou, 2016). These therapies have greatly improved the survival and quality of NSCLC patients. After a variable length of time from starting treatment, the resistance mechanisms of first- and second- generation EGFR-TKIs inevitably emerge. The T790M mutation at exon 20 within the kinase domain of EGFR is the most common mechanism of acquired resistance, which occurs in approximately 50–60% of EGFR-TKIresistant tumors
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