Abstract CT009: IMbrave150: Updated efficacy and safety by risk status in patients (pts) receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment for unresectable hepatocellular carcinoma (HCC)

Abstract Background: Based on the Ph III IMbrave150 trial, atezo + bev has been approved globally and is the standard of care for pts with unresectable HCC who have not received prior systemic therapy. With an additional 12 mo of follow-up from the primary analysis (median, 15.6 mo), atezo + bev showed consistent clinically meaningful treatment benefit and safety (Finn ASCO GI 2021). Here, we report results of updated analyses considering high-risk factors. Methods: Pts were randomized 2:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg PO BID until loss of clinical benefit or unacceptable toxicity. High-risk pts were defined as those who had tumor invasion of the main trunk of the portal vein and/or the portal vein branch contralateral to the primarily involved lobe (Vp4), and/or bile duct invasion and/or tumor occupancy of ≥ 50% of liver. Results: In the ITT population, 64 (19%) pts randomized to atezo + bev and 37 (22%) pts randomized to sor were defined as high risk. 10 pts had bile duct invasion, 73 had Vp4 portal vein invasion and 31 had liver tumor occupancy of ≥ 50%. 9 pts in the atezo + bev arm and 4 pts in the sor arm had 2 high-risk factors. OS, PFS and ORR all favored atezo + bev over sor, in both non-high-risk and high-risk patients. See table for efficacy results. In safety-evaluable pts, Grade 3/4 treatment-related AEs (TRAEs) occurred in 122 (45%) of 269 non-high-risk and 21 (35%) of 60 high-risk atezo + bev pts. Grade 5 TRAEs occurred in 5 (2%) non-high-risk and 1 (2%) high-risk atezo + bev pt. Conclusions: Efficacy benefit was seen with atezo + bev vs sor regardless of the presence of high-risk features. HRs remained similar despite the numerical differences in median OS between non-high-risk and high-risk pts. Further, the overall safety data in the atezo + bev arm were comparable between non-high-risk and high-risk pts and in line with the known safety profile of each drug. Non-High RiskHigh RiskITTAtezo + BevSorAtezo + BevSorAtezo + BevSorEvaluable for OS/PFS, n2721286437336165Median OS (95% CI), mo22.8 (19.1, 24.9)15.7 (13.2, 19.0)7.6 (6.6, 12.8)5.5 (4.1, 6.7)19.2 (17.0, 23.7)13.4 (11.4, 16.9)HR (95% CI)0.68 (0.51, 0.91)0.62 (0.39, 1.00)0.66 (0.52, 0.85)Median PFS (95% CI), moa7.2 (6.5, 9.6)4.4 (4.0, 5.8)5.4 (4.0, 6.9)2.8 (2.5, 5.3)6.9 (5.7, 8.6)4.3 (4.0, 5.6)HR (95% CI)0.61 (0.48, 0.78)0.74 (0.47, 1.17)0.65 (0.53, 0.81)Evaluable for ORR, n2631246335326159Confirmed ORR, n (%)a,b81 (31)13 (10)16 (25)5 (14)97 (30)18 (11)Complete response, n (%)a20 (8)05 (8)1 (3)25 (8)1 (1)Median DOR (95% CI), moa,c19.0 (14.6, NE)12.6 (4.9, 17.0)16.3 (13.5, NE)16.5 (3.9, NE)18.1 (14.6, NE)14.9 (4.9, 17.0)NCT03434379.Clinical cutoff date: Aug 31, 2020.DOR, duration of response; HR, hazard ratio; IRF, independent review facility; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.aAssessed by an IRF per RECIST 1.1.bORR IRF RECIST 1.1-evaluable population was based on patients who presented with measurable disease at baseline.cDOR analysis was based on all confirmed responders. Citation Format: Richard S. Finn, Shukui Qin, Masafumi Ikeda, Peter R. Galle, Michel Ducreux, Tae-You Kim, Masatoshi Kudo, Ho Yeong Lim, Valeriy Breder, Philippe Merle, Ahmed Kaseb, Daneng Li, Yin-Hsun Feng, Wendy Verret, Alan Nicholas, Lindong Li, Ning Ma, Andrew X. Zhu, Ann-Lii Cheng. IMbrave150: Updated efficacy and safety by risk status in patients (pts) receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment for unresectable hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT009.