Abstract 6684: Impact of fecal microbiome on the efficacy of neoadjuvant chemo-immunotherapy and colitis adverse events: Findings from the NADIM II Trial

Abstract

Abstract Introduction: The balance and composition of the gut microbiome play a pivotal role in modulating the host immune system, and they have been associated with survival outcomes in patients undergoing immunotherapy-based treatments and immune-related adverse events. In this study, our objective was to analyze the fecal microbiota of non-small-cell lung cancer (NSCLC) patients with locally advanced disease undergoing neoadjuvant chemo-immunotherapy (IO-CT). Methods and patients: Baseline stool samples were collected from 86 resectable stage IIIA/B NSCLC patients enrolled in the NADIM II clinical trial (NCT03838159). The patients were randomly assigned to receive either neoadjuvant nivolumab plus chemotherapy (CT) or CT alone. DNA extraction was performed using the QIAamp PowerFecal DNA Kit (Qiagen), and the samples were analyzed using the Ion AmpliSeq Microbiome Health Research assay (ThermoFisher). The NGS analysis utilized the AmpliSeq Microbiome Health w1.3 workflow. Alpha diversity was assessed using the Simpson and Chao1 Index. Results: Among the 86 collected stool samples, 77 were deemed valid for analysis. Bacteroides were the most common genus with a relative percentage (RP) of 18.9% ± 14.8 followed by Faecalibacterium (13.4% ± 7.8). The presence of bacteria from the genera Bifidobacterium, and Faecalibacterium was associated with improved progression-free survival (PFS) [HR = 0.4 (0.16-0.98), and HR = 0.08 (0.01-0.72), respectively] and overall survival (OS) [HR = 0.19 (0.06-0.62)], and HR = 0.04 [0.01-0.43], respectively), in the experimental arm. The detection of Faecalibacterium prausnitzii (validated by qPCR) was associated with improved PFS [HR = 0.17 (0.04-0.76)] and OS [HR = 0.05 (0.01-0.29)] in the experimental. On the other hand, detection of bacteria from the genera Synergistes, Lactobacillus, and Anaerotruncus was associated to higher risk of disease progression [HR = 9.9 (1.2-85), HR = 3.7 (1.5-9.1), and HR = 12 (1.4-110)] and death [HR = 51 (3.2-820), HR = 6.7 (2-23), and HR = 25 (2.3-280)] in this set of patients.In the entire cohort, patients whose samples were in the highest tertile of alpha diversity, had significantly prolonged PFS compared to those with intermediate or low diversity [HR = 0.39 (0.16-0.94)]. Finally, 25 colitis adverse events (CAE) occurred in 18 patients, including two Grade 3 (2.3%) and four Grade 2 (4.6%) events. A higher RP of Bacteroides were found in patients who did not suffer colitis events (P = 0.016), whereas higher RP of Coriobacterium were detected in patients who suffered CAE (P = 0.023). Conclusions: Our findings suggest that composition of the gut microbiome may play a crucial role in the effectiveness of neoadjuvant IO-CT in NSCLC patients. Specifically, the presence of F. prausnitzii may enhance the antitumor activity of these treatments. Citation Format: Roberto Serna-Blasco, Alejandro Rodriguez Festa, Sandra Sanz-Moreno, Lucía Robado de Lope, Pilar Mediavilla Medel, Ernest Nadal, Jose Luis González Larriba, Alex Martínez-Martí, Reyes Bernabé, Joaquim Bosch-Barrera, Joaquín Casal-Rubio, Virginia Calvo, Amelia Insa, Santiago Ponce, Noemí Reguart, Javier de Castro, Joaquín Mosquera, Manuel Cobo, Andrés Aguilar, Carlos Camps, Rafael López de Castro, Teresa Morán, Isidoro Barneto, Delvys Rodríguez-Abreu, Carlos Aguado de la Rosa, Ramón Palmero, Florentino Hernando-Trancho, Javier Martín-López, Alberto Cruz-Bermúdez, Bartomeu Massuti, Miguel Ángel Molina Vila, Atocha Romero, Mariano Provencio. Impact of fecal microbiome on the efficacy of neoadjuvant chemo-immunotherapy and colitis adverse events: Findings from the NADIM II Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6684.