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Observational Study
. 2024 Sep;55(3):1388-1400.
doi: 10.1007/s12029-024-01095-7. Epub 2024 Jul 30.

Concomitant Medications Alter Clinical Outcomes in Patients with Advanced Digestive Tract Cancer Receiving PD-1 Checkpoint Inhibitors Combined with Antiangiogenetic Agents

Yiran Wang #  1 , Zhiheng Wu #  1 , Xudong Zhu #  2 , Yu Zheng  1 , Yanyan Yang  1 , Jinming Tu  3 , Hongming Pan  1 , Xian Zhong  4 , Weidong Han  5 , Junlin Yao  6
Affiliations
Observational Study

Concomitant Medications Alter Clinical Outcomes in Patients with Advanced Digestive Tract Cancer Receiving PD-1 Checkpoint Inhibitors Combined with Antiangiogenetic Agents

Yiran Wang et al. J Gastrointest Cancer. 2024 Sep.

Abstract

Purpose: Our study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination.

Methods: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC).

Results: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death.

Conclusion: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.

Keywords: Concomitant medication; Gastrointestinal cancer; Hepatocellular cancer; Immunotherapy-antiangiogenesis combination; Prognostic factor.

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