Abstract 1076P
Background
Cancer cachexia is a multifactorial syndrome that involves immune-metabolic crosstalk across multiple organs and has been associated with a negative clinical impact of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). In parallel, the gut microbiota has emerged as one of the “hallmarks of cancer” and a key contributor to ICI response. However, the association of the cachexia with gut microbiota and their impact on ICI response remain unexplored.
Methods
In this observational prospective study, we included 113 Japanese patients with NSCLC treated with ICI monotherapy or chemoimmunotherapy. Fecal samples were collected prior to ICI initiation and 16S rRNA gene sequence was performed. Microbiota composition was analyzed based on patient’s cancer cachexia status, change in weight after ICI initiation as well as PFS and OS.
Results
The incidence of cachexia was 50.4% and the median PFS and OS were significantly shorter in the cachexia group than in the non-cachexia group [4.3 vs. 11.6 months (P = 0.003) and 12.0 months vs not reached (NR) (P = 0.02), respectively]. Multivariable analysis revealed that cachexia at baseline was independently associated with shorter PFS. Taking into consideration the cachexia patients, subgroup analysis revealed that gain in body weight from the baseline (cachexia-reversible) was associated with significantly longer PFS and OS. Microbiota composition revealed different bacteria clusters between patients with and without cachexia. Patients with cachexia had overrepresentation of commensal bacteria Escherichia-Shigella and Hungatella, while patients in the non-cachexia group had increased representation of Blautia, Agathobacter, Anaerostipes and Eubacterium ventriosum.
Conclusions
We demonstrated that cachexia and longitudinal bodyweight change had prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, we observed different microbiota compositions between patients with and without cachexia. This study provides insights for the development of therapeutic strategies combining interventions into cachexia or microbiota in patients amenable to ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
JSPS KAKENHI.
Disclosure
Y. Okuma: Financial Interests, Personal, Invited Speaker: Astra Zenca, 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. Y. Hosomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Taiho Pharmaceutical, Kyowakirin, Takeda, Nippon Kayaku, Eisai, Novartis. B. Routy: Financial Interests, Personal, Advisory Board: BMS, Merck, Vedanta, Kaleido, AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca, Merck, Davolterra, Kaleido, Imagia. All other authors have declared no conflicts of interest.