LBA7 - Randomised efficacy and safety results for atezolizumab (Atezo) + bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)

Abstract

BackgroundPts 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. MethodsArms 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). ResultsIn 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.Table: LBA7Unlabelled ImageArm FIRF RECIST 1.1IRF HCC mRECISTF1 Atezo + Bev n = 60F2 Atezo n = 59aF1 Atezo + Bev n = 60F2 Atezo n = 59aMedian follow up, mo6.66.76.66.7Median PFS, mo5.6b3.4b5.63.495% CI3.6 – 7.41.9 – 5.23.6 – 7.41.9 – 5.2HR 80% CI0.55b0.40 – 0.74P = 0.01080.540.40 – 0.74Arm A: Atezo + Bev n = 104IRF RECIST 1.1IRF HCC mRECISTMedian follow up, mo12.4Confirmed ORR, n (%)37 (36)b41 (39)95% CI26 – 4630 – 50CR12 (12)16 (15)PR25 (24)25 (24)On-going response28 (76)28 (68)DCR (CR + PR + SD), n (%)74 (71)74 (71)Median DOR, moNENE95% CI11.8 – NE11.8 – NEMedian PFS, mo7.37.395% CI5.4 – 9.95.4 – 9.9Data cut off: 14 Jun 2019.a1 randomised pt did not receive atezo.bPrimary endpoint. ConclusionsBy 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 identificationNCT02715531. Editorial acknowledgementJonathan Lee, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the studyF. Hoffmann-La Roche, Ltd. FundingF. Hoffmann-La Roche, Ltd. DisclosureC. 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.