From: The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies
Study | Tumor (n) | Checkpoint inhibitor | Findings | References |
---|---|---|---|---|
PS | Metastatic melanoma (n = 43) | Anti-PD-1 therapy (agent and dose not specified) | Higher diversity of gut microbiome in R (n = 30) vs. NR (13, p < 0.01), not observed in oral microbiome Enrichment of Clostridiales order/Ruminococcaceae family in R vs. enrichment of Bacteroides thetaiotaomicron, Escherichia coli, and Anaerotruncus colihominis in NR, not observed in oral microbiome Median PFS undefined with high vs. 242 days with low abundance of Faecalibacterium genus (p = 0.03); median PFS 188 days with high vs. median PFS 393 days with low abundance of Bacteroidales order (p = 0.05) | [19] |
RS | Advanced NSCLC (n = 60), RCC (n = 40) | Anti-PD-1 therapy (agent and dose not specified) | Akkermansia muciniphila was significantly enriched in R vs. NR (validated in subsequent cohort with 27 NSCLC and 26 RCC pts) In the NSCLC cohort, A. muciniphila was also enriched in R (p = 0.045 with/without antibiotics, p = 0.026 excluding antibiotic-treated) along with Ruminococcus spp., Alistipes spp., Eubacterium spp., Bifidobacterium adolescentis, Bifidobacterium longum, and Parabacteroides distasonis | [20] |
PS | Metastatic melanoma (n = 26) | I3 or 10 mg/kg Q3 weeks → maintenance Q12 weeks | In 7 pts with immune-related colitis, significant reductions from baseline to time of colitis seen in Firmicutes phylum (Ruminococcus, Lachnospiracea incertae sedis, Blautia, Clostridium IV, Eubacterium, unclassified Lachnospiraceae and Pseudoflavonifractor) and colitis associated with decreased bacterial diversity Baseline enrichment in Faecalibacterium genus and Firmicutes phylum (unclassified Ruminococcaceae, Clostridium XIVa and Blautia) significantly associated with longer PFS (p = 0.0039) and OS (p = 0.051) vs. Bacteroides spp. (independent of clinical characteristics) Baseline enrichment with Firmicutes phylum significantly associated with developing colitis (p = 0.009) vs. Bacteroidetes phylum in those who did not develop colitis (p = 0.011) | [24] |
PS | Metastatic melanoma (n = 39) | I3 mg/kg Q3 weeks X4 doses, N 1 mg/kg + I3 mg/kg Q3 weeks X4 doses → N 240 mg Q2 weeks, N 240 mg Q2 weeks, or P 2 mg/kg Q3 weeks | In all pts: Baseline enrichment with Bacteroides caccae (p = 0.032 and Streptococcus parasanguinis (p = 0.048) in R vs. NR In N + I arm: Baseline enrichment with Firmicute phylum (Faecalibacterium prausnitzii (p = 0.032) and Holdemania filiformis (p = 0.043)) and Bacteroidetes phylum [Bacteroides thetaiotamicron (p = 0.046)] in R vs. NR In P arm, baseline enrichment with Dorea formicigenerans (p = 0.045) in R vs. NR In all pts, 83 gut metabolites at baseline were significantly different in R vs. NR (49 increased, 34 decreased, p < 0.05) | [25] |
RS | Locally advanced or metastatic NSCLC (n = 15) | N 3 mg/kg Q2 weeks | 73.3% received antibiotic monotherapy, 53.3% antibiotic duration > 7 days, 53.3% received antibiotics 1–3 months before first N, 33.4% < 1 month, and 13.3% during N Rate of CR 26.7%, SD 33.3%, PD 40% in antibiotic-treated vs. rate of CR 22%, SD 27.1%, PD 50.9% in non-antibiotic-treated (p = 0.75) No impact of antibiotics on PFS under N (p = 0.72) | [22] |
RS | Advanced RCC (n = 16) or NSCLC (n = 48) | Anti-PD-1 or anti-PD-L1 antibody ± anti-CTLA-4 antibody (agents and dose not specified) | In RCC, PD rate 75% vs. 22% (p < 0.01), median PFS 1.9 vs. 7.4 months (HR 3.1, 95% CI 1.4–6.9, p < 0.01), median OS 17.3 vs. 30.6 months (HR 3.5, 95% CI 1.1–10.8, p = 0.03) in antibiotic-treated vs. no antibiotics (up to 30 days) In NSCLC, PD rate 52% vs. 43% (p = 0.26), median PFS 1.9 vs. 3.8 months (HR 1.5, 95% CI 1.0–2.2, p = 0.03), median OS 7.9 vs. 24.6 months (HR 4.4, 95% CI 2.6–7.7, p < 0.01) in antibiotic-treated vs. no antibiotics (up to 30 days) | [23] |
RS | Metastatic melanoma (n = 42) | Anti-PD-1 or anti-CTLA-4 therapy (agent and dose not specified) | 8 spp. more abundant at baseline in R: Enterococcus faecium, Collinsella aerofaciens, Bifidobacterium adolescentis, Klebsiella pneumoniae, Veillonella parvula, Parabacteroides merdae, Lactobacillus spp., and Bifidobacterium longum 2 spp. more abundant at baseline in NR: Ruminococcus obeum and Roseburia intestinalis | [21] |