LBA7Randomised efficacy and safety results for atezolizumab (Atezo) + bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC). (24th November 2019)

• Record Type: Journal Article
• Authors: Hsu, C-H; Lee, M S; Lee, K-H; Numata, K; Stein, S; Verret, W; Hack, S; Spahn, J; Liu, B; Huang, C; He, R; Ryoo, B-Y
• Is Part Of: Annals of oncology. Volume 30(2019)Supplement 9
• Publication Date: 2019-11-24
• Subjects: Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz446.006
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: Pts with unresectable HCC have few treatment (tx) options. Checkpoint inhibitors and combination approaches with anti-VEGFs are emerging as potential new tx options. Here we report the first randomised dataset evaluating atezo (anti-PD-L1) as monotherapy vs the combination of atezo + bev (anti-VEGF; Arm F) as well as updated single-arm atezo + bev data (Arm A) from a Ph 1b study. Methods: Arms F and A of the Ph 1b study GO30140 enrolled systemic tx-naïve pts with unresectable HCC. Arm F pts were randomised 1:1 to atezo + bev or atezo monotherapy and received atezo 1200 mg IV q3w +/- bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo + bev. Primary endpoints were progression free survival (PFS; Arm F) and objective response rate (ORR, Arm A) by independent review facility (IRF)-assessed RECIST 1.1, and safety (Arms F and A). Results: In Arm F, 60 pts were randomised to atezo + bev (Group F1) and 59 pts to atezo (Group F2). Arm F showed a statistically significant improvement in the primary endpoint median PFS for atezo + bev vs atezo (5.6 vs 3.4 mo, HR 0.55, 80% CI, 0.40 – 0.74, P = 0.0108). Any-Gr TRAEs occurred in 41 (68%) F1 pts and 24 (41%) F2 pts; Gr 3-4 TRAEs occurred in 12 (20%) F1 pts and 3 (5%) F2 pts. There were no Gr 5 TRAEs in Arm F. For the 104 pts in Arm A, primary endpoint ORR was 36% (37 pts) with 76% of responses ongoing. Any-Grade (Gr) tx-related adverse events (TRAEs) occurred in 91 (88%) pts; Gr 3-4 TRAEs occurred in 41 (39%) pts. Gr 5 TRAEs were seen in 3 (3%) pts. Conclusions: By meeting its primary endpoint of improved PFS for atezo + bev vs atezo alone, Arm F showed the single-agent contribution of atezo and bev to the overall tx effect. With longer follow up, Arm A highlights the clinically meaningful and durable responses of atezo + bev. Coupled with a tolerable safety profile, these data suggest that atezo + bev is a promising first-line tx option for unresectable HCC. Clinical trial identification: NCT02715531. Editorial acknowledgement: Jonathan Lee, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Funding: F. Hoffmann-La Roche, Ltd. Disclosure: C. Hsu: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): MSD; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche. M.S. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): BMS; Research grant / Funding (self): Pfizer; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Genentech/Roche. K. Lee: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AZ; Advisory / Consultancy: Bayer; Advisory / Consultancy: Ono Pharmaceutical; Advisory / Consultancy: Samsung Bioepis; Advisory / Consultancy: Eisai. S. Stein: Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Exelixis. W. Verret: Full / Part-time employment: Genentech. S. Hack: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. J. Spahn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. B. Liu: Full / Part-time employment: Genentech. C. Huang: Full / Part-time employment: Roche. R. He: Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai Inc; Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy, Research grant / Funding (institution): Merck & Co; Advisory / Consultancy: AZ.