Abstract 1147P
Background
The gut microbiota is an immune-specific biomarker of cancer immunotherapy. Antibiotic- or antacid-induced dysbiosis negatively impacts clinical outcomes of immunotherapy. However, the impact of dysbiosis on the efficacy of chemoimmunotherapy, the standard of care in first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC), remains unknown. Therefore, this study aimed to evaluate the impact of chemoimmunotherapy in patients with NSCLC exposed to antibiotics or antacids.
Methods
We retrospectively reviewed patients with advanced NSCLC who were treated with first-line chemoimmunotherapy between 2018 and 2020 at the National Cancer Center Hospital. Patients harboring oncogenic alterations after the failure of treatment with tyrosine kinase inhibitors were also included. The nearest neighbor propensity score matching method was used to reduce potential confounding factors. We analyzed clinical outcomes including progression-free survival (PFS), and overall survival (OS).
Results
Of the 201 eligible patients, 21 with antibiotics (ABx) and 42 without ABx (Non-ABx) were identified after propensity score matching. No differences were observed between the two groups in PFS (ABx vs. Non-ABx, median: 6.0 vs. 6.4 months; p=0.656) and OS (20.4 vs. 23.4 months; p=0.900). On the other hand, 27 patients from this cohort received antacids and 36 patients did not, and the OS was significantly shorter in patients with antacids than in those without antacids (17.3 months vs. Not reached; p=0.004). In addition, there was a trend toward significance suggesting that the PFS was shorter in patients with antacids (4.8 vs. 6.7 months; p=0.065). Table: 1147P
| Meian PFS | Before matching (ABx=33, Non-ABx=168) | After matching (ABx=21, Non-ABx=42) | ||
| ABx | 6.9 | HR 1.10 (95%CI 0.71-1.70) | 6 | HR 0.87 (95%CI 0.46-1.63) |
| Non-ABx | 7.5 | 6.4 | ||
| Meian OS | ||||
| ABx | 26.3 | HR 1.53 (95%CI 0.90-2.60) | 20.4 | HR 0.95 (95%CI 0.43-2.08) |
| Non-ABx | 37.1 | 23.4 | ||
| Meian PFS | Before matching (PPI/H2B=99, Non-PPI/H2B=103) | After matching (PPI/H2B=27, Non-PPI/H2B=36) | ||
| PPI/H2B | 6.8 | HR 1.30 (95%CI 0.94-1.80) | 4.8 | HR 1.73 (95%CI 0.97-3.09) |
| Non-PPI/H2B | 8.6 | 6.7 | ||
| Median OS | ||||
| PPI/H2B | 24.8 | HR 1.67 (95%CI 1.08-2.57) | 17.3 | HR 2.95 (95%CI 1.40-6.21) |
| Non-PPI/H2B | 37.1 | Not reached |
Conclusions
The use of antacids is associated with the prognostic factors of chemoimmunotherapy, whereas the use of antibiotics is not.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Okuma: Financial Interests, Personal, Invited Speaker: AstraZeneca, K. K., Nippon Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Eli Lilly K. K., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie, G.K., Chugai Co., Ltd. K. Masuda: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., AstraZeneca, K. K., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb. Y. Shinno: Financial Interests, Personal, Invited Speaker: BMS, Chugai, AstraZeneca, Eli Lilly, Ono; Financial Interests, Personal, Research Grant: Ono, Janssen, Japan Clinical Research Operations K.K. T. Yoshida: Financial Interests, Personal, Invited Speaker: AstraZeneca, Taiho, Chugai, Novartis, Eli Lilly, MSD, Ono, Roche, ArcherDX, BMS; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Takeda, Daiichi Sankyo, Ono, MSD, AbbVie, Novartis, Chugai, BMS; Financial Interests, Personal, Stocks/Shares: MSD, AstraZeneca, Novartis, Amgen, Chugai. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Ono Pharmaceutical, Thermo Fischer, Pfizer, Taiho; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Guardant Health, Preferred Network; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Prefered Network. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku; Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, Ono Pharmaceutical, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AbbVie. N. Yamamoto: Financial Interests, Personal, Research Grant: Astellas, AstraZeneca, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, Ono, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi; Non-Financial Interests, Personal, Advisory Role: Eisai; Non-Financial Interests, Personal, Advisory Board: Takeda, Otsuka, Boehringer Ingelheim, Cimic, Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Ono, Chugai, Sysmex, Daiichi Sankyo, Eisai. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Ono, BMS, Eli Lilly, Boehringer Ingelheim, Takeda, MSD, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celltrion, Amgen, Nippon Kayaku, Takeda, Pfizer, Ono, Janssen, AnHeart Therapeutics Inc; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, Ono; Non-Financial Interests, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.