IMbrave150: Exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients (pts) with main trunk and/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in a global Ph III study.

Abstract

4073 Background: Atezo + bev has been approved in >60 countries for pts with unresectable HCC who have not received prior systemic therapy, based on IMbrave150 (NCT03434379; Finn RS NEJM 2020). Due to their poor prognosis and the hemodynamic changes from increased portal vein pressure, pts with main portal vein tumor thrombus are often excluded from pivotal HCC trials. Here, we report exploratory efficacy and safety results of pts with Vp4 (presence of a tumor thrombus in the main trunk and/or contralateral portal vein) using updated IMbrave150 data (Finn RS ASCO GI 2021). Methods: Pts were randomized 2:1 to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. IMbrave150 enrolled 501 systemic treatment (tx)–naive unresectable HCC pts, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1, including 73 (15%) Vp4 pts. This post hoc exploratory analysis was conducted with a median follow-up of 15.6 mo in ITT pts. Results: Of the Vp4 pts, 48 received atezo + bev and 25 received sor. Median OS (mOS) was 7.6 vs 5.5 mo (HR, 0.62; 95% CI: 0.34, 1.11) and median PFS (mPFS) per independent review facility (IRF)–assessed RECIST 1.1 was 5.4 vs 2.8 mo (HR, 0.62; 95% CI: 0.35, 1.09) with atezo + bev and sor, respectively. ORR per IRF RECIST 1.1 was 23% (11/47) with atezo + bev (2 [4%] pts had CR) vs 13% (3/23) with sor (1 [4%] pt had CR). All-grade variceal bleeding was higher with atezo + bev in Vp4 (13.6%) vs rest of ITT pts (2.5%). See table for further efficacy and safety data. Conclusions: The benefits of atezo + bev over sor in Vp4 pts are consistent with those in ITT pts across all efficacy endpoints, despite the expected disease-intrinsic increase in variceal bleeding in Vp4 vs rest of ITT pts. The overall positive benefit-risk profile supports the use of atezo + bev in pts with Vp4. Clinical trial information: NCT03434379. [Table: see text]

Changing the Treatment Paradigm for Hepatocellular Carcinoma Using Atezolizumab plus Bevacizumab Combination Therapy

“…Furthermore, the ORR was 23% and 31% for the Vp4 and non-Vp4 groups, while the CR rate was 4% and 8% for the Vp4 and non-Vp4 groups, respectively. Thus, while the Vp4 group remained slightly inferior to the non-Vp4 group, it exhibited a high response rate that has not been observed with previous molecularly targeted agents [30]. Additionally, while the natural course for Vp4 cases was roughly 3 months [31,32], the use of the atezolizumab plus bevacizumab combination therapy extended that to 7.6 months, which was a clinically meaningful improvement in OS.…”

“…Sub-analysis studies have reported the favorable effects of atezolizumab plus bevacizumab combination therapy in high-risk groups with poor prognoses in IMbrave150, such as those with (1) portal vein invasion at the main portal branch (Vp4), (2) a tumor occupancy rate of over 50%, and (3) bile duct infiltration cases [29]. In particular, the analysis of the Vp4 group was quite interesting because no background differences were observed between groups with or without Vp4 and, except for the Vp4 presence, the OS hazard ratio was similar to the non-Vp4 group (Vp4 group: 0.62, non-Vp4 group: 0.67), where 60% (29/48) of Vp4 patients had extrahepatic spread as well [30]. Moreover, both the groups with and without Vp4 presented equivalent effects on PFS (Vp4 group, PFS HR: 0.62; non-Vp4 group, PFS HR: 0.67).…”

Efficacy and safety of chemoradiation therapy using one-shot cisplatin via hepatic arterial infusion for advanced hepatocellular carcinoma with major macrovascular invasion: a single-arm retrospective cohort study

“…Systemic chemotherapy, such as atezo + beva, is effective for advanced HCC [ 10 , 23 ] and for HCC with Vp. However, the prognosis remains poor, with 67% of patients alive 6 months after the initiation of treatment with atezo + beva [ 24 , 25 ]. Kudo et al reported that MVI is a factor leading to poor outcomes in patients with advanced HCC because MVI rapidly worsens flow in the portal vein and leads to liver failure and portal hypertension [ 10 ].…”

“…Systemic chemotherapy, such as the combination of atezolizumab plus bevacizumab (atezo + beva), is effective for patients with advanced HCC [ 10 , 22 , 23 ] and for patients with HCC with portal vein invasion (Vp), but the overall survival (OS) of patients with Vp was less than that of patients without Vp [ 23 – 25 ]. The poor prognosis of patients with Vp is a result of major MVI that causes deterioration in the preserved hepatic function and portal hypertension, and interferes with the administration of chemotherapy [ 10 ].…”

“…The poor prognosis of patients with Vp is a result of major MVI that causes deterioration in the preserved hepatic function and portal hypertension, and interferes with the administration of chemotherapy [ 10 ]. However, atezo + beva take 2.8 months to obtain a response, and 20% of the recipients of these agents are non-responders [ 23 – 25 ].…”