O-8 Atezolizumab + bevacizumab vs sorafenib for unresectable hepatocellular carcinoma: Results from older adults enrolled in IMbrave150

Data regarding the efficacy and safety of systemic therapies in older adults with hepatocellular carcinoma (HCC) are limited. In the phase III IMbrave150 trial, atezolizumab + bevacizumab was associated with statistically significant and clinically meaningful improvements in overall survival (OS; HR, 0.58; 95% CI: 0.42, 0.79) and progression-free survival (PFS; HR, 0.59; 95% CI: 0.47, 0.76) as well as clinically meaningful delays in deterioration of patient-reported functioning and quality of life (QoL) vs sorafenib in patients with unresectable HCC who had not received prior systemic therapy (Cheng, ESMO Asia, 2019). Here, we report exploratory subgroup analyses of the efficacy, safety and patient-reported outcome (PRO) results for older adults enrolled in IMbrave150. IMbrave150 randomized 501 systemic treatment (tx)–naïve patients with unresectable HCC. Patients were randomized 2:1 to receive either atezolizumab 1200 mg IV q3w + bevacizumab 15 mg/kg IV q3w or sorafenib 400 mg BID until unacceptable toxicity or loss of clinical benefit per investigator. Co-primary endpoints were OS and PFS by independent review facility (IRF)-assessed RECIST 1.1. Objective response rate (ORR) per IRF-RECIST 1.1 and time to deterioration (TTD) in patient-reported physical functioning, role functioning and QoL per the EORTC QLQ-C30 questionnaire were pre-specified secondary endpoints. The exploratory older adult subgroup was defined to include those aged ≥ 65 years. In IMbrave150, 161 (48%) patients enrolled in the atezolizumab + bevacizumab arm and 91 (55%) in the sorafenib arm were aged ≥ 65 years. In these patients, the median OS was not reached with atezolizumab + bevacizumab vs 14.9 months with sorafenib (HR, 0.58; 95% CI: 0.36, 0.92). The median PFS was 7.7 months with atezolizumab + bevacizumab vs 4.8 months with sorafenib (HR, 0.63; 95% CI: 0.45, 0.89). ORRs were 26% with atezolizumab + bevacizumab vs 13% with sorafenib, with 7 and 0 patients achieving complete responses, respectively. TTD in physical functioning (HR, 0.48; 95% CI: 0.32, 0.73), role functioning (HR, 0.61; 95% CI: 0.40, 0.91) and QoL (HR, 0.71; 95% CI: 0.47, 1.07) were longer for patients receiving atezolizumab + bevacizumab vs sorafenib. In the atezolizumab + bevacizumab arm, 62 of 158 (39%) treated patients aged ≥ 65 years experienced a grade 3-4 treatment-related AE (TRAE) and 4 (3%) patients experienced a grade 5 TRAE, whereas 55 of 171 (32%) treated patients aged < 65 years experienced a grade 3-4 TRAE and 1 (1%) patient experienced a grade 5 TRAE. Exploratory analyses were also conducted with the subgroup of patients aged ≥ 70 years, showing similar results for efficacy, safety and PROs. Similar to the IMbrave150 ITT population, older adults with previously untreated, unresectable HCC derived a clinically meaningful benefit from atezolizumab + bevacizumab vs sorafenib. Additionally, treatment with atezolizumab + bevacizumab showed a delay in deterioration in patient-reported functioning and QoL vs sorafenib. Safety of atezolizumab + bevacizumab in adults ≥ 65 years old is generally consistent with the safety in younger patients, with no added risks or toxicities.