The association of antibiotic use and survival among patients receiving first line immunotherapy-based treatment for advanced gastroesophageal cancers.

Abstract

349 Background: The advent of immune checkpoint inhibition (ICI) has improved the survival for patients with gastroesophageal cancer (GEC). It is vital to understand the relationship between the tumor microenvironment and the ability of the immune system to prevent and eliminate cancer cells. Antibiotics (abx), frequently used in patients on cancer-directed therapy, can alter gut microbiota leading to dysbiosis and altered immune responses. Some research shows its use is associated with decreased ICI efficacy in RCC, NSCLC, and melanoma. The goal of our study is to investigate the association of abx timing and survival with 1L ICI-based treatments for advanced GEC. Methods: The retrospective, multicenter analysis used the Flatiron Health deidentified electronic health record-derived database of real world (rw) patients with advanced esophageal, GEJ, and gastric cancers (EC/GEJC/GC) who received ICI +/- chemotherapy (chemo) as 1L therapy. Abx exposure was defined by antibiotic use from 42 days before to 42 days after starting ICI. The cox proportion hazards models were used to compare rw overall survival (OS) and progression-free survival (PFS) across exposure groups. Results: A total of 990 patients were included for the main group analysis with comparison of survival and abx usage and timing: 876 did not receive abx, 58 received abx within 42 days after starting ICI, and 56 received abx within 42 days prior to starting ICI. The median age was 66 with 44.4% EC, 33.5% GC, and 22% GEJC. The majority of patients had adenocarcinoma (87.9%). The unadjusted OS HR for abx (within 42 days) before ICI was 0.99 (0.68-1.46, p=0.971) and (within 42 days) after ICI was 1.56 (1.11-2.19, p=0.011), suggesting worse OS with abx use after ICI initiation. HR trended towards worse PFS for those receiving abx after 1L ICI [1.36 (0.97-1.90 p= 0.073)]. In subgroup analysis, the negative effect of starting abx after 1L ICI over abx before ICI was more prominent in those receiving ICI monotherapy compared to those receiving chemo/ICI. Conclusions: Our study identifies a poorer survival association of abx administration after 1L ICI-based therapy for advanced GEC, primarily driven by ICI monotherapy. Main group comparison between abx usage and timing: OS Abx Use/Timing n (%) HR No 876 (88.5) Yes, after 1L IO 58 (5.9) 1.56 (1.11-2.19, p=0.011) Yes, before 1L IO 56 (5.7) 0.99 (0.68-1.46, p=0.971) Subgroup comparison between abx usage and timing by treatment type Chemo + IO: OS Yes, after 1L IO 44 (6.9) 1.32 (0.88-1.98,p=0.177) Yes, before 1L IO 38 (6.0) 1.01 (0.62-1.65, p=0.964) IO monotherapy: OS Yes, after 1L IO 12 (4.9) 2.64 (1.38-5.06, p=0.003) Yes, before 1L IO 12 (4.9) 1.09 (0.53-2.23, p=0.810)