Abstract 5952: Modulating treatment outcomes of patients with solid tumors in immunotherapy trials: a drug interaction analysis from a phase I unit

Abstract The concurrent use of medications can either compromise or enhance treatment (Tx) outcomes in patients with solid tumors (pts) receiving immunotherapy compounds (IO) including monoclonal antibodies (Abs), fusion proteins (FP), immune modulators (IM), oncolytic viruses (OV) and vaccines (VAC). To assess the impact of concurrent medications on Tx outcomes, we conducted a retrospective analysis of pts enrolled in early IO clinical trials at the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center between June 2014 and June 2024. A computerized data extraction tool was used to collect clinical data and identify the prescription of a predefined set of drugs within 30 days of the experimental IO infusion. Primary endpoints were median overall survival (mOS) and median progression-free survival (mPFS), defined as the time from first Tx cycle to death/last follow up or disease progression/death from any cause, respectively. Tumor responses were assessed according to RECIST; disease control rate (DCR) was defined as the proportion of pts achieving partial response (PR) or stable disease (SD) as the best response. Uni and multivariate analysis were performed to correlate variables and outcomes. A total of 827 pts were included (49.3% female, 50.7% male), with the median age of 58 years (range 20-85). The majority of pts (72.9%) were White/Caucasian. The most common tumor types were colorectal (24.5%), head/neck (10.5%) and pancreatic (9.4%), and 85.7% of pts had >2 metastatic sites. The most commonly used therapies were Abs and FP (64.7%) and IM (20.8%), followed by IM + Abs combination (9.2%), OV and VAC (5.3%). The median time from the first appointment to death was 9.26 mo (range 0.85-112). mOS was 6.14 mo (range 0.16-103) and mPFS 2.07 mo (range 0-37.8). Of 744 pts with evaluable response data, the DCR was 38.7%. For IM + Abs, SD and PR were 24% and 6% without antihistamines (AH) and 52% and 15.8% with AH (X2 8.48; p = 0.014). Univariate analyses identified higher body mass index (BMI) and cancer type (immune responsive versus immune insusceptible) associated with improved OS while low albumin level, presence of cancer pain, and use of steroids, proton pump inhibitors (PPI), antibiotics (ATB), anti-depressants, anti-emetics, anticoagulant and narcotics were related to worse OS (p < 0.05). Multivariate analysis adjusted for BMI, cancer type, albumin level and response to Tx revealed that AH were associated with improved OS (HR 0.752 [0.603, 0.938], p = 0.012) while steroids (HR 1.413 [1.101, 1.814], p = 0.007), PPI (HR 1.318 [1.02, 1.703], p = 0.035) and ATB (HR 1.542 [1.222, 1.947], p < 0.001) were related to worse OS. In conclusion, concurrent use of medications must be carefully evaluated as part of clinical trial protocols for experimental IO. Optimizing the management of drug prescriptions could improve patient outcomes and enhance the efficacy of experimental Tx. Citation Format: Camila Braganca Xavier, Clark Andersen, JoAnn T. Lim, Julian H. Slade, Stacie A. Bean, Lei Kang, Hung Le, Apostolia Tsimberidou, Aung Naing, David Hong, Ecaterina Dumbrava, Jordi Rodon, Paula Pohlmann, Sarina Piha-Paul, Stephane Champiat, Timothy A. Yap, Tin-Yun Tang, Funda Meric-Bernstam, Siqing Fu. Modulating treatment outcomes of patients with solid tumors in immunotherapy trials: a drug interaction analysis from a phase I unit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5952.