Baseline symptom, health status, and health utilities in patients in early-phase clinical trials combining immune checkpoint blockade with other anticancer therapies.
Authors: George Goldy C , Piha-Paul Sarina A. , Fu Siqing , Rodon Ahnert Jordi , Yap Timothy A. , Subbiah Vivek , Dumbrava Ecaterina Elena , Tsimberidou Apostolia Maria , Pant Shubham , Appleton Grace , Noor Laila , Meric-Bernstam Funda , Cleeland Charles S. , Mendoza Tito R. , Hong David S. 
Published: June 2023

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Background: The overall goal of our prospective and longitudinal study (NCI R01CA242565) is to examine the use of patient report to evaluate symptomatic adverse events associated with combination treatment including at least one immune checkpoint inhibitor in early-stage clinical trials. We present here the baseline symptom, health status and utilities in patients prior to trial start, and their association with clinical factors. Methods: Patients scheduled to start an early-phase trial of combination treatment with at least one immune checkpoint inhibitor and who had not received clinical trial-related treatment completed the validated MD Anderson Symptom Inventory - Immunotherapy (0-10, higher scores = worse severity) and the validated EuroQoL-5 dimensions questionnaire including a visual analog scale (EQ5D VAS) (0-100, higher scores = better health status) and health utility items (e.g., self-care, mobility). Clinical data were extracted from the EMR. Statistical tests included Spearman’s correlation coefficients. Results: At baseline prior to start of trial-related treatment, 38% of patients (N = 164; median age = 60 y; 52% male; 85% White; 17% ECOG PS 0, 89% ECOG PS 1, 3% ECOG PS 2) experienced at least 1 severe symptom (≥7 on 0-10 scale). The most frequent severe baseline symptoms were pain (21% of patients), fatigue (17%), disturbed sleep (15%), drowsiness (12%), lack of appetite (10%), distress (10%), and pain in the abdomen (10%). Less than 2% of pts experienced severe immunotherapy-specific symptoms of rash, fever/chills and swelling of the hands and feet at baseline. Moderate-severe symptom-related interference (≥4 on 0-10 scale) was worst for activity (40% of patients), work (38%), and enjoyment of life (30%). For the EQ5D health utility dimensions, patients reported the most problems with pain or discomfort (75%) and fewest problems with self-care (10%). Worse composite symptom severity (P = 0.013) and worse problems with activity (P = 0.001) and pain (P = 0.012) were associated with worse and higher ECOG PS. Worse symptom severity (-0.54, P < 0.001), symptom interference with activity- (-0.57, P < 0.001) and mood- (-0.42, P < 0.001) related functioning were associated inversely with superior health status. Worse symptom interference with activity-related functioning was linked with lower concurrent lymphocyte counts (P = 0.01), hemoglobin (P = 0.01) and serum albumin (P = 0.004) levels and higher platelet (P = 0.02) counts. Conclusions: Patients in early-phase trials that combine immunotherapy with other anti-cancer therapies may experience severe symptom burden and symptom interference with functioning, even at baseline prior to treatment start. Thus, it is important to baseline symptoms to fully understand the impact of combination treatments including checkpoint inhibitors in early-stage clinical trials.