Use of yttrium-90 (Y90) glass microspheres (TheraSphere) as neoadjuvant to transplantation/resection in hepatocellular carcinoma: Analyses from the LEGACY study.

Abstract

300 Background: The objective of the LEGACY study was to assess the Objective Response Rate (ORR) and Duration of Response (DoR) following treatment with Yttrium-90 (Y90) glass microspheres in patients with unresectable solitary hepatocellular carcinoma (HCC). The objective of the analyses presented here are to evaluate ORR, DoR, and Overall Survival (OS) by transplant/resection status and to compare these outcomes with patients who did not go on to transplantation/resection after receiving treatment with Y90. Methods: LEGACY is a single-arm, multicenter, retrospective study of patients with unresectable HCC who received treatment with Y90 glass microspheres (TheraSphere) at one of three sites in the United States. LEGACY included all consecutive eligible patients who received treatment between January 2014 and December 2017 and met the eligibility criteria (Child-Pugh A; ECOG score of 0 or 1; BCLC A or C; and a solitary tumor > 2 and ≤8 cm). Primary efficacy endpoints included ORR and DoR. ORR included patients who achieved either a complete response or partial response based on localized mRECIST; response was assessed via blinded, independent, central review. Secondary endpoints include OS and number and type of subsequent treatments, including transplantation and resection. Results: Among all 162 patients enrolled in LEGACY, ORR was 72.2% (117/162; 95% CI = 64.9%, 78.5%); the majority of patients experienced DoR ≥ 6 months (89/117, 76.1%, 95% CI = 67.6%, 82.9%). Median follow-up time for all 162 patients enrolled in LEGACY was 29.9 months by reverse Kaplan-Meier analysis; 3-year OS was 86.6%. For 45/162 (27.8%) of patients, Y90 treatment served as neoadjuvant therapy; 34 went on to transplantation (21.0%) and 11 (6.8%) went on to resection. For neoadjuvant treatment, ORR was 80.0% (36/45, 95% CI = 66.2, 89.1), DoR ≥ 6 months was 30.6% (11/45, 95% CI = 18.0, 46.9), and 3-year OS was 92.8% (95% CI = 74.2, 98.2). Of these 45 patients, 35 patients achieved complete response (CR), 1 achieved partial response (PR), and 9/45 (20.0%) were deemed not evaluable as they underwent surgery prior to the 6-month mark and did not have imaging assessments post-Day 46. These nine patients were censored, lowering the DoR; however, histopathology revealed that 7/9 (77.8%) achieved complete pathologic necrosis, 1/9 (11.1%) had extensive pathologic necrosis, and 1 (11.1%) had partial pathologic necrosis. For the 117/162 (72.2%) patients who did not go on to surgical treatment, ORR was 91.5% (107/117, 95% CI = 85.0, 95.3), DoR ≥ 6 months was 72.9% (78/117, 95% CI = 63.8, 80.4), and 3-year OS was 83.5% (95% CI = 72.2, 90.5). Conclusions: Treatment of solitary unresectable HCC with Y90 glass microspheres provides strong ORR, DoR, and OS both as neoadjuvant therapy to transplantation/resection and as treatment in non-surgical candidates.