(P 130) HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH RESECTABLE RETROPERITONEAL DEDIFFERENTIATED LIPOSARCOMA (DDLPS) TREATED WITH NEOADJUVANT CHECKPOINT BLOCKADE IN A RANDOMIZED PHASE II CLINICAL TRIAL.

Objective: In SARC028, patients with DDLPS had a 1~0% overall response rate to pembrolizumab. We conducted a randomized, phase II, non-comparative trial of neoadjuvant combination nivolumab (nivo) and ipilimumab (ipi/nivo). Here, we report data on the health-related quality of life (HRQoL) metrics and adverse events.

Methods: In this study (NCT03307616), patients with resectable retroperitoneal DDLPS were randomized (1:1) to receive three doses of nivo (3mg/kg) or one dose of combination nivo (3 mg/kg) and ipi (1 mg/kg) followed by two doses of nivolumab (3mg/kg). 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 one post-baseline assessment. Analyses included mean change from baseline scores to weeks 7 and 54. Adverse events (AE) were tracked while patients received treatment and in the post-operative period.

Results: Overall, 17 patients were randomized from October 2017 to February 2020. Seven (88%) patients treated with nivo and 8 (89%) ipi/nivo patients reported adverse events, with the majority of AEs occurring while on- treatment. HRQoL were collected at baseline and at week 7 for six (75%) nivo and seven (78%) ipi/nivo patients. Four (50%) nivo and 7 (78%) ipi/nivo patients completed postoperative week 54 assessments. MDASI scores indicative of symptom severity and interference of daily life decreased by 0.9 and 0.8 from 1.1 and 1.5 for patients undergoing nivo while they increased by 0.5 and 0.5 from 0.4 and 0.6 for patients undergoing combination agent therapy at 54 weeks. Both arms had similar increases at 7 weeks. Patients undergoing combination agent therapy with ipi/nivo experienced decline in EORTC-QLC global health status at both 7 and 54 weeks (-6.0, -15.5). Patients undergoing single agent therapy with nivo experienced an initial decline in global health status followed by significant recovery (-2.8, 16.7). The mean change in total FACT-G score did not differ between the nivo vs ipi/nivo arms at 7 weeks (1.9 vs 5) or at 54 weeks (11.6 vs 9.8). The decline in global health status mirrored the trends in AEs with the ipi/nivo patients experiencing 33 AEs compared to 14 AEs in the nivo patients while on treatment. Patients who received combination therapy also experienced more AEs in the immediate post-operative period (10 vs 6) and at 54 weeks (20 vs 5).

Conclusion: For patients with resectable DDLPS, single agent immune checkpoint blockade with nivolumab is associated with greater improvement in long term HRQoL and fewer adverse events compared to combination ipi/nivo therapy. Dual checkpoint inhibition was associated with decline in HRQoL preoperatively at 7 weeks post treatment, ongoing loss in global health status at 54 weeks post treatment, and more AEs during the treatment and post treatment periods. This is similar to our previously reported findings of poor recovery to baseline function and continued decline of HRQoL in patients with undifferentiated pleomorphic sarcoma undergoing ip/nivo/XRT.