Abstract C067: Patient-reported baseline symptomatic adverse events in early-phase trials of combination treatments with immune checkpoint blockade, and their association with concurrent global health status, health utilities and clinical factors
Authors: George Goldy C. , Piha-Paul Sarina A , Fu Siqing , Dumbrava Ecaterina , Subbiah Vivek , Tsimberidou Apostolia , Blumenschein George , Pant Shubham , Appleton Grace , Noor Laila , Ahnert Jordi Rodon , Yap Timothy , Meric-Bernstam Funda , Cleeland Charles , Mendoza Tito , Hong David S 
Published: December 2023

Abstract
Background: We examined patient-reported symptomatic adverse events (AEs) prior to trial start, and their association with concurrent global health status, health utilities and clinical factors in patients enrolled in early-phase trials combining immune checkpoint blockade with other anticancer therapy.
Methods: Within 2 weeks prior to trial start, patients consented to begin an early phase trial of a combination treatment including at least 1 immune checkpoint inhibitor completed validated items of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measuring severity and/or frequency of selected symptomatic adverse events (score range: 0-4, higher scores=worse severity/increased frequency) in the last 7 days. Patients also completed the validated EuroQoL-5 dimensions questionnaire measuring global health status (score range: 0-100, higher scores=better health status) and health utilities (e.g., problems with self-care, mobility). Clinical data were extracted from the EMR. Statistical tests included χ2 and Spearman’s correlations.
Results: 206 patients (median age=59y; 54% male; 84% White) from 54 early-phase trials participated. Prevalent moderate-to-severe symptomatic AEs at baseline prior to trial start included fatigue (43% of patients), decreased sexual interest (24%), appetite loss (21%), dry mouth (17%) and shortness of breath (16%). Frequent-to-almost constant general pain, abdominal pain and nausea were reported by 27%, 13% and 5% of patients, respectively. Worse fatigue, and more frequent general pain and abdominal pain were associated with diminished global health status (P&lt;0.001 for each). Worse fatigue was also linked to problems with mobility, self-care, anxiety, and usual activities (P&lt;0.001 for each), and to lower concurrent lymphocyte counts (P=0.002), hemoglobin (P=0.002) and serum albumin (P=0.029). Loss of appetite was related to lower lymphocytes (P=0.005), platelets (P=0.011), and serum albumin (P=0.021) and higher neutrophils (P=023). Dyspnea was linked to lower albumin (P=0.014). Loss of sexual interest was associated with worse pain (P&lt;0.001), anxiety (P=0.011), and problems with usual activities (P&lt;0.001), lower serum albumin (0.005), lymphocytes (P=0.010), hemoglobin (0.019), and creatinine (P=0.03) and higher neutrophils (P=0.009) and white blood cells (0.023).
Conclusions: Patients in early-phase trials of combination treatments with an immune checkpoint inhibitor may report considerable moderate-to-severe symptomatic AEs, even at baseline. Patient-reported symptomatic AEs impact global health status, health utilities, and a constellation of clinical factors. Thus, it is critical in early-phase trials to baseline symptomatic AEs including from the patient’s perspective in order to more completely assess the impact of combination treatments that include a checkpoint inhibitor.
Citation Format: Goldy C. George, Sarina A Piha-Paul, Siqing Fu, Ecaterina Dumbrava, Vivek Subbiah, Apostolia Tsimberidou, George Blumenschein, Shubham Pant, Grace Appleton, Laila Noor, Jordi Rodon Ahnert, Timothy Yap, Funda Meric-Bernstam, Charles Cleeland, Tito Mendoza, David S Hong. Patient-reported baseline symptomatic adverse events in early-phase trials of combination treatments with immune checkpoint blockade, and their association with concurrent global health status, health utilities and clinical factors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C067.