Abstract 138P
Background
Faecalibacterium prausnitzii is one of the most prevalent commensals within the gut microbiota, being one of the gut's major butyrate-producing bacteria. Recent studies suggest a potential role for F. prausnitzii in exerting anti-tumorigenic effects.
Methods
In the context of the phase II NADIM II clinical trial, a total of 81 baseline stool from locally advanced non-small cell lung cancer (NSCLC) patients randomized into the experimental arm (neoadjuvant nivolumab plus chemotherapy followed by adjuvant nivolumab, n=55) or the control arm (chemotherapy alone, n=26) were collected. DNA was extracted using the QIAamp PowerFecal DNA Kit (Qiagen) and analyzed by QPCR using specific primers for F. prausnitzii strain ATCC 27768.
Results
In the experimental arm, the presence of F.prautnizzi was significantly associated with improved overall survival (HR: 0.24; 95CI: 0.08-0.76; P=0.015), and a trend was noted toward progression-free survival (HR: 0.46; 95IC: 0.18-1.19; P=0.1). Specifically, patients with detected F. prausnitzii in their fecal sample (n=46) exhibited a 88% probability of being alive and 68% of having no evidence of disease, compared to 55% and 44%, respectively, in patients with undetectable F. prausnitzii (n=9). Notably, this observation was not evident in the control arm (P=0.425 and P=0.812 for PFS and OS, respectively). A trend was also observed regarding PDL1 expression. The percentage of tumors expressing PD-L1 was 66% in patients with detected F. prausnitzii, compared to of 29% in the F. prausnitzii-negative population (P=0.062).
Conclusions
The presence of Faecalibacterium prausnitzii is associated with improve survival outcomes in NSCLC patients with locally advanced disease treated with perioperative nivolumab and chemotherapy.
Clinical trial identification
NCT03838159.
Legal entity responsible for the study
Spanish Group of Lung Cancer.
Funding
This study was funded by Bristol Myers Squibb. The study was also supported by the European Union Horizon 2020 Research and Innovation program under grant agreement no. 875160. In addition, the project received funds from Instituto de Salud Carlos III (ISCIII) PI19/01652, PI21/01500 (Co-funded by European Regional Development Fund/ European Social Fund ‘A way to make Europe’/‘Investing in your future’) and grant RTC2019-007359-1 (BLI- O) from the Ministry of Science and Innovation. A.C-B. is supported by Sara Borrell fellowship grant n° CD19/00170. Instituto de Salud Carlos III (ISCIII).
Disclosure
E. Nadal: Financial Interests, Institutional, Funding: Nanostring, Roche, Bristol Myers Squibb and Merck Serono; Financial Interests, Institutional, Other, Consulting fees: Roche, AstraZeneca, Bristol Myers Squibb, Merck Sharpe & Dohme, Merck Serono, Sanofi, Amgen, Lilly, Pfizer, Takeda, Boehringer Ingelheim and Bayer; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, AstraZeneca, Bristol Myers Squibb, Merck Sharpe & Dohme, Merck Serono, Sanofi, Amgen, Lilly, Pfizer, Takeda, Boehringer Ingelheim and Bayer; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Roche, MSD and Pfizer; Financial Interests, Institutional, Advisory Board: Apollomics; Financial Interests, Institutional, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Member of the Steering Committee of the Spanish Lung Cancer Group. J.L. Gonzalez-Larriba: Financial Interests, Institutional, Funding:MSD, Janssen-CILAG, AstraZeneca, Roche and MIRATTI; Financial Interests, Institutional, Other, Consulting fees:MSD, AstraZeneca, MIRATTI and Janssen CILAG; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events:MSD, Roche, BMS, Janssen CILAG and AstraZeneca; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Pfeizer, MSD and AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca, Sanofi and Takeda. A. Martinez-Marti: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche AG, Merck Sharp & Dohme, MSD Oncology and Pfizer; Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche AG, Merck Sharp & Dohme, MSD Oncology and Pfizer; Financial Interests, Institutional, Expert Testimony: AstraZeneca/MedImmune; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: AstraZeneca/MedImmune, Bristol Myers Squibb, F. Hoffmann La Roche AG, Merck Sharp & Dohme, MSD Oncology, Pfizer and Lilly; Financial Interests, Institutional, Advisory Board: AstraZeneca/MedImmune; Financial Interests, Institutional, Other, Steering Committee Member: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Other, Participation on a Data Safety Monitoring Board or Advisory Board: F. Hoffmann La Roche AG and Bristol Myers Squibb. R. Bernabe Caro: Financial Interests, Institutional, Funding: Investigational Grant Roche; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, BMS, Pfizer, MSD, Amgen, Takeda and AstraZeneca; Financial Interests, Institutional, Advisory Board: Takeda, Roche, BMS and AstraZeneca. J. Bosch-Barrera: Financial Interests, Institutional, Funding: Pfizer and Roche; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, MSD, Sanofi, AstraZeneca, Pfizer and Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche and MSD. V. Calvo de Juan: Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, BMS, MSD, AstraZeneca, Takeda, Pfizer, Lilly and Boehringer Ingelheim; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Takeda and Lilly. M.A. Insa Molla: Financial Interests, Personal, Other, Consulting fees: Pfizer, Amgen and AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bristol Myers Squibb, Roche, Pfizer, AstraZeneca and Takeda; Financial Interests, Institutional, Advisory Board: Roche and BMS. N. Reguart Aransay: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Amgen, Lilly, Sanofi, MSD, BMS, Takeda, Novartis, AstraZeneca and Janssen. J. de Castro Carpeño: Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb, Merk Sharp & Dohme, Hoffmann-La Roche; Financial Interests, Institutional, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merk Sharp&Dohme, Hoffmann-LA Roche, Pfizer, Takeda, GSK, Janssen, Sanofi, Bayer and Lilly; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merk Sharp&Dohme, Hoffmann-La Roche, Pfizer, Takeda, Sanofi and Bayer. B. Massuti Sureda: Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Other, Consulting fees: Roche, Bristol Myers Squibb, Boehringer Ingelheim and Takeda; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Bristol Myers Squibb, Takeda, Merck Sharpe and Dohme. A. Romero: Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Thermofisher Scientific. Bristol Myers Squibb Foundation and Takeda; Financial Interests, Personal, Other, Patents: nº EP 22 382 701.5 (pending); Financial Interests, Institutional, Funding: PI21/01500 (PI), PI19/01652, RTC2019-007359-1 (BLI- O), Bristol Myers Squibb, H2020 European Institute of Innovation and Technology (875160); Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Illumina, Health in code and Thermofisher. M. Provencio Pulla: Financial Interests, Institutional, Funding: H2020 European Institute of Innovation and Technology (875160), Instituto de Salud Carlos III (PI19/01652), Instituto de Salud Carlos III (PI21/01500), Ministerio de Ciencia e Innovación (RTC2019-007359-1), Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting fees: BMS, AstraZeneca, MSD, Roche, Takeda; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, AstraZeneca, MSD, Roche, Takeda; Financial Interests, Personal, Other, Support for attending meetings and/or travel: BMS, AstraZeneca, MSD, Roche, Takeda; Financial Interests, Personal, Other, Patents: n° EP 22 382 701.5 (pending). All other authors have declared no conflicts of interest.