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.
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).
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% 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.
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.
NCT02715531.
Medical writing assistance was provided by Steffen Biechele, PhD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
F. Hoffmann-La Roche, Ltd.
M. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): Bristol-Myers Squibb ; Research grant / Funding (self): Pfizer; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Genentech/Roche. C. Hsu: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Research grant / Funding (self): MSD; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: AZ; Advisory / Consultancy: Roche. S. Stein: Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Exelixis. W. Verret: Full / Part-time employment: Genentech/Roche. S. Hack: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. J. Spahn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. B. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech/Roche. H. Abdullah: Full / Part-time employment: Genentech/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. K. Lee: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Ono Pharmaceuticals; Honoraria (self), Speaker Bureau / Expert testimony: Roche; Honoraria (self): Samsung Bioepis; Speaker Bureau / Expert testimony: Eli Lilly. All other authors have declared no conflicts of interest. LBA39 DCR, disease control rate; DOR, duration of response; NE, not estimable; SD, stable disease. Data cut off: 14 June 2019. 1 randomised pt did not receive atezo. Primary endpoint.Arm F IRF RECIST 1.1 IRF HCC mRECIST F1 Atezo + Bev (n = 60) F2 Atezo (n = 59)a F1 Atezo + Bev (n = 60) F2 Atezo (n = 59)a Median follow-up, mo 6.6 6.7 6.6 6.7 Median PFS, mo 95% CI 5.6b 3.6 – 7.4 3.4b 1.9 – 5.2 5.6 3.6 – 7.4 3.4 1.9 – 5.2 HR 0.55b 0.54 80% CI 0.40 – 0.74 P = 0.0108 0.40 – 0.74 Arm A: Atezo + Bev n = 104 IRF RECIST 1.1 IRF HCC mRECIST Median follow-up, mo 12.4 Confirmed ORR, n (%) 37 (36)b 41 (39) 95% CI (%) 26 – 46 30 – 50 Complete Response (CR), n (%) 12 (12) 16 (15) Partial Response (PR), n (%) 25 (24) 25 (24) On-going response, n (%) 28 (76) 28 (68) DCR (CR + PR + SD), n (%) 74 (71) 74 (71) Median DOR, mo NE NE 95% CI 11.8 – NE 11.8 – NE Median PFS, mo 7.3 7.3 95% CI 5.4 – 9.9 5.4 – 9.9