- Email: [email protected]
Randomised efficacy and safety results for atezolizumab (Atezo) + bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
abstracts
Annals of Oncology
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
C-H. Hsu1, M.S. Lee2, K-H. Lee3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, C. Huang8, R. He9, B-Y. Ryoo10 1 Oncology, National Taiwan University Hospital, Taipei, Taiwan, 2UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3Department of Education and Training, Seoul National University Hospital, Seoul, Republic of Korea, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5Medical Oncology, Yale School of Medicine, New Haven, CT, USA, 6Product Development - Oncology, Genentech, Inc., South San Francisco, CA, USA, 7Biostatistics PDBB, Genentech, Inc., South San Francisco, CA, USA, 8 Safety Science Oncology, Roche Product Development, Shanghai, China, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 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-PDL1) as monotherapy vs the combination of atezo þ bev (anti-VEGF; Arm F) as well as updated single-arm atezo þ bev data (Arm A) from a Ph 1b study. Methods: Arms F and A of the Ph 1b study GO30140 enrolled systemic tx-naı¨ve pts with unresectable HCC. Arm F pts were randomised 1:1 to atezo þ bev or atezo monotherapy and received atezo 1200 mg IV q3w þ/- bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints were progression free survival (PFS; Arm F) and objective response rate
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.
Table: LBA7 Arm F IRF RECIST 1.1
IRF HCC mRECIST
F1 Atezo þ Bev n ¼ 60
F2 Atezo n ¼ 59
F1 Atezo þ Bev n ¼ 60
F2 Atezo n ¼ 59a
6.6 5.6b 3.6 – 7.4
6.7 3.4b 1.9 – 5.2
6.6 5.6 3.6 – 7.4
6.7 3.4 1.9 – 5.2
Median follow up, mo Median PFS, mo 95% CI HR 80% CI
a
0.55b 0.40 – 0.74 P ¼ 0.0108
0.54 0.40 – 0.74 Arm A: Atezo þ Bev n ¼ 104
IRF RECIST 1.1 Median follow up, mo Confirmed ORR, n (%) 95% CI CR PR On-going response DCR (CR þ PR þ SD), n (%) Median DOR, mo 95% CI Median PFS, mo 95% CI
IRF HCC mRECIST 12.4
37 (36)b 26 – 46 12 (12) 25 (24) 28 (76) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
41 (39) 30 – 50 16 (15) 25 (24) 28 (68) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
Data cut off: 14 Jun 2019. a 1 randomised pt did not receive atezo. b Primary endpoint.
Volume 30 | Supplement 9 | November 2019
doi:10.1093/annonc/mdz446 | ix187
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz446.006/5638776 by University of Connecticut user on 16 December 2019
LBA7
(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 þ 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 þ bev vs atezo (5.6 vs 3.4 mo, HR 0.55, 80% CI, 0.40 – 0.74, P ¼ 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 þ 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 þ bev. Coupled with a tolerable safety profile, these data suggest that atezo þ 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.
Annals of Oncology
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
C-H. Hsu1, M.S. Lee2, K-H. Lee3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, C. Huang8, R. He9, B-Y. Ryoo10 1 Oncology, National Taiwan University Hospital, Taipei, Taiwan, 2UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3Department of Education and Training, Seoul National University Hospital, Seoul, Republic of Korea, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5Medical Oncology, Yale School of Medicine, New Haven, CT, USA, 6Product Development - Oncology, Genentech, Inc., South San Francisco, CA, USA, 7Biostatistics PDBB, Genentech, Inc., South San Francisco, CA, USA, 8 Safety Science Oncology, Roche Product Development, Shanghai, China, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea 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-PDL1) as monotherapy vs the combination of atezo þ bev (anti-VEGF; Arm F) as well as updated single-arm atezo þ bev data (Arm A) from a Ph 1b study. Methods: Arms F and A of the Ph 1b study GO30140 enrolled systemic tx-naı¨ve pts with unresectable HCC. Arm F pts were randomised 1:1 to atezo þ bev or atezo monotherapy and received atezo 1200 mg IV q3w þ/- bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints were progression free survival (PFS; Arm F) and objective response rate
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.
Table: LBA7 Arm F IRF RECIST 1.1
IRF HCC mRECIST
F1 Atezo þ Bev n ¼ 60
F2 Atezo n ¼ 59
F1 Atezo þ Bev n ¼ 60
F2 Atezo n ¼ 59a
6.6 5.6b 3.6 – 7.4
6.7 3.4b 1.9 – 5.2
6.6 5.6 3.6 – 7.4
6.7 3.4 1.9 – 5.2
Median follow up, mo Median PFS, mo 95% CI HR 80% CI
a
0.55b 0.40 – 0.74 P ¼ 0.0108
0.54 0.40 – 0.74 Arm A: Atezo þ Bev n ¼ 104
IRF RECIST 1.1 Median follow up, mo Confirmed ORR, n (%) 95% CI CR PR On-going response DCR (CR þ PR þ SD), n (%) Median DOR, mo 95% CI Median PFS, mo 95% CI
IRF HCC mRECIST 12.4
37 (36)b 26 – 46 12 (12) 25 (24) 28 (76) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
41 (39) 30 – 50 16 (15) 25 (24) 28 (68) 74 (71) NE 11.8 – NE 7.3 5.4 – 9.9
Data cut off: 14 Jun 2019. a 1 randomised pt did not receive atezo. b Primary endpoint.
Volume 30 | Supplement 9 | November 2019
doi:10.1093/annonc/mdz446 | ix187
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz446.006/5638776 by University of Connecticut user on 16 December 2019
LBA7
(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 þ 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 þ bev vs atezo (5.6 vs 3.4 mo, HR 0.55, 80% CI, 0.40 – 0.74, P ¼ 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 þ 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 þ bev. Coupled with a tolerable safety profile, these data suggest that atezo þ 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.