Health-related quality of life in patients with resectable undifferentiated pleomorphic sarcoma treated with neoadjuvant checkpoint blockade in a single institution randomized phase II clinical trial.
Authors: Lyu Heather G. , Lillemoe Heather A. , Chiang Yi-Ju , Keung Emily Zhi-Yun , Nguyen Sa Thi , Peterson Susan K. , Torres Keila E , Hunt Kelly , Feig Barry W. , Bishop Andrew Justin , Guadagnolo Beverly Ashleigh , Somaiah Neeta , Roland Christina Lynn , Scally Christopher 
Published: June 2022

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Background: In SARC028, patients with undifferentiated pleomorphic sarcoma (UPS) had a 40% overall response rate to pembrolizumab. Based on this, we conducted a randomized, phase II, non-comparative trial of combination nivolumab (nivo/RT) and ipilimumab (ipi/nivo/RT) and demonstrated an 89% major pathologic response. Here, we report the health-related quality of life (HRQoL) metrics. Methods: In this study (NCT03307616), patients with resectable UPS were randomized (1:1) to receive one dose of nivo (3mg/kg) or one dose of combination nivo (3 mg/kg) and ipi (1 mg/kg), followed by combination of nivo (3 doses, 3mg/kg every 2 weeks) plus 50 Gy in 25 fractions (both arms). HRQoL was assessed using the MD Anderson Symptom Inventory (MDASI), European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30, and the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaires. Questionnaire completion rates were calculated using the number of patients with at least one baseline and post-baseline assessment. Analyses included mean change from baseline scores to week 11 (preoperative) and week 54 (postoperative). Results: Ten patients were randomized from October 2017 to February 2020. HRQoL were collected at baseline (n = 10) and at week 11 for five (83%) nivo/RT and three (60%) ipi/nivo/RT patients. Three (60%) nivo/RT and three (100%) ipi/nivo/RT patients had week 54 assessments. MDASI scores indicative of symptom severity and interference of daily life both decreased for patients undergoing ipi/nivo/RT (0.8→0.67 and 0.9→0.46, respectively) while both increased in the nivo/RT group (1.6→2.22 and 1.9→3.33, respectively). Both arms had similar increases at 54 weeks. Patients undergoing ipi/nivo/RT experienced a greater decline in EORTC-QLC global health status at 54 weeks than those undergoing single agent therapy (-22.92 vs -8.33). The mean change in total FACT-G score did not differ between the two arms at 11 weeks (-4.0 vs -4.5), however, there was a significant decline for patients undergoing ipi/nivo/RT at 54 weeks (-20.3 vs -5.7). Conclusions: For patients with resectable UPS, combination immune checkpoint blockade with ipi/nivo/RT is associated with an improvement in short term HRQoL compared to single-agent nivo/RT. This finding warrants further study with more patients, controlling for baseline symptom scores. Combination therapy was associated with a slower recovery to baseline function, with ongoing decline in HRQoL at 54 weeks post treatment. Our study demonstrates the feasibility of collecting HRQoL metrics, which can be key factors in guiding patient management decisions. Clinical trial information: NCT03307616.