- Email: [email protected]
CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)
abstracts Pharmaceutical, Lilly, MSD, Novartis; Honoraria (self): Bristol-Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme; Research grant / Funding (institution): Ono Pharmaceutical, AstraZeneca, MSD, Genentech. I. Xynos: Shareholder / Stockholder / Stock options: Bristol-Myers Squibb. M. Kodani: Shareholder / Stockholder / Stock options: Ono Pharmaceutical Co. Ltd. Y. Kitagawa: Honoraria (self): Ethicon, Olympus, Ono Pharmaceutical, Tahi Pharmaceutical, Chugai Pharma, Nippon Kayaku, Asahi Kasei; Research grant / Funding (institution): Astellas, Otsuka, Kaken Pharmaceutical, Kyowa Hakko Kirin, Kowa, CSL Behring, Shionogi, Saiichi Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Tsumura & Co., Teijin Pharma, Medtronic, Boehringer Ingelheim, Merck Serono, Novartis, Ajinomoto, Asahi Ka. All other authors have declared no conflicts of interest.
CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)
T. Yau1, J.W. Park2, R.S. Finn3, A-L. Cheng4, P. Mathurin5, J. Edeline6, M. Kudo7, KH. Han8, J.J. Harding9, P. Merle10, O. Rosmorduc11, L. Wyrwicz12, E. Schott13, S.P. Choo14, R.K. Kelley15, D. Begic16, G. Chen17, J. Neely18, J. Anderson19, B. Sangro20 1 Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China, 2 Department of Cancer Control and Population Health, NCC-GCSP, Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea, 3Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 4Department of Internal Medicine, National Taiwan University Hospital Cancer Center, Taipei, Taiwan, 5Service d’He´patologie, Centre Hospitalo-Universitaire Claude Huriez, Lille, France, 6Medical and Digestive Oncology, Centre Eugene - Marquis, Rennes, France, 7Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan, 8Internal Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea, 9Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10Hepatology Unit, Hoˆpital de la Croix-Rousse, Lyon, France, 11 Hepatogastroenterology, Assistance Publique Hoˆpitaux de Paris, Hoˆpital Pitie´Salpe´trie`re – Universite´ Pierre et Marie Curie, Paris, France, 12Department of Gastrointestinal Cancer, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 13Internal Medicine II - Gastroenterology, Hepatology and Diabetology, Helios Klinikum Emil von Behring GmbH, Klinik fu¨r Innere Medizin II, Berlin, Germany, 14Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 15Medicine, University of California San Francisco Parnassus Campus, San Francisco, CA, USA, 16Global Clinical Research/Immuno-Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 17GBS - Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 18 Immuno-Oncology Biomarker Lead for HCC & SCCHN, Bristol-Myers Squibb, Princeton, NJ, USA, 19Immuno-Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 20 Hepatology, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain Background: SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to prolong survival and improve tolerability. This phase III study compared clinical efficacy and safety of NIVO with SOR as 1L therapy in pts with aHCC. Methods: Systemic therapy–naive pts aged 18 years with aHCC were randomized 1:1 to NIVO (240 mg IV Q2W) or SOR (400 mg oral BID). Primary endpoint was overall survival (OS). Additional endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review per RECIST v1.1, efficacy by tumor programmed death ligand 1 (PD-L1) expression, and safety. Results: 743 pts with aHCC were randomized to NIVO (n ¼ 371) or SOR (n ¼ 372) with minimum follow-up of 22.8 months at data cutoff. OS did not meet the predefined threshold of statistical significance (HR 0.84, P ¼ 0.0419). Median OS (mOS) was 16.4 mo for NIVO and 14.7 mo for SOR (HR 0.85 [95% CI: 0.72–1.02]; P ¼ 0.0752). Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region (Asia vs non-Asia). ORR was 15% for NIVO (14 pts with complete response [CR]) and 7% for SOR (5 pts with CR; Table). Grade 3/4 treatment-related adverse events were reported in 81 pts (22%) in the NIVO arm and 179 pts (49%) in the SOR arm and led to discontinuation in 16 (4%) and 29 (8%) pts, respectively. No new safety signals were observed with NIVO. 140 pts (38%) in the NIVO arm and 170 pts (46%) in the SOR arm received subsequent therapy. Additional OS analyses and patient-reported outcomes will be presented to support the benefit of NIVO.
v874 | Gastrointestinal tumours, non-colorectal
Table: LBA38_PR Efficacy results NIVO n ¼ 371 Median OS (95% CI), mo 16.4 (13.9–18.4) 12-mo OS rate, % (95% CI) 59.7 (54.4–64.6) 24-mo OS rate, % (95% CI) 36.8 (31.8–41.8) Median PFS, mo (95% CI) 3.7 (3.1–3.9) ORR, n (%) 57 (15) BOR, n (%) Complete response 14 (4) Partial response 43 (12) ORR by baseline tumor PD-L1 expression, n/n (%) PD-L1 1% 20/71 (28) PD-L1 <1% 36/295 (12)
SOR n ¼ 372 14.7 (11.9–17.2) 55.1 (49.8–60.1) 33.1 (28.3–38.0) 3.8 (3.7–4.5) 26 (7) 5 (1) 21 (6) 6/64 (9) 20/300 (7)
Conclusions: Though the primary endpoint of OS did not achieve statistical significance vs SOR, NIVO showed clinically meaningful improvements in OS, ORR, and CR rate as 1L treatment for aHCC. NIVO demonstrated a favorable safety profile consistent with previous reports. Clinical trial identification: NCT02576509. Editorial acknowledgement: Writing and editorial assistance was provided by Andrea L. Hammons of Parexel International (Waltham, MA, USA) and funded by BristolMyers Squibb. Legal entity responsible for the study: Bristol-Myers Squibb. Funding: Bristol-Myers Squibb. Disclosure: T. Yau: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb. R.S. Finn: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Honoraria (self), Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Roche/ Genentech. A. Cheng: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Merck Sharp Dohme; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin; Speaker Bureau / Expert testimony: Amgen Taiwan; Advisory / Consultancy: Ispen; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. P. Mathurin: Honoraria (self), Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: Bayer Healthcare ; Honoraria (self), Speaker Bureau / Expert testimony: AbbVie; Honoraria (self), Speaker Bureau / Expert testimony: Gilead; Honoraria (self), Speaker Bureau / Expert testimony: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi. J. Edeline: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony: IPSEN; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Travel / Accommodation / Expenses: Amgen. M. Kudo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Ono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medico’s Hirata; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): EA Pharma; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Gilead. J.J. Harding: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony: Elly Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: CytomX; Honoraria (self), Speaker Bureau / Expert testimony: QED. P. Merle: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: AstraZeneca. O. Rosmorduc: Honoraria (self): Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Sirtex; Honoraria (self): Eisai. L. Wyrwicz: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Beigene; Research grant / Funding (self): Eisai. E. Schott: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bayer. S.P. Choo: Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Sirtex; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, IDMC membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding
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Annals of Oncology
Annals of Oncology (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Parttime employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
M. Lee1, B-Y. Ryoo2, C-H. Hsu3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, H. Abdullah8, R. He9, K-H. Lee10 1 UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5 Medical 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, 8Safety Science Oncology, Genentech, Inc., South San Francisco, CA, USA, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Internal Medicine, Seoul National University Hospital, 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, bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints
Volume 30 | Supplement 5 | October 2019
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 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% 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: Medical writing assistance was provided by Steffen Biechele, 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: M. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): BristolMyers 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.
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abstracts
CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)
T. Yau1, J.W. Park2, R.S. Finn3, A-L. Cheng4, P. Mathurin5, J. Edeline6, M. Kudo7, KH. Han8, J.J. Harding9, P. Merle10, O. Rosmorduc11, L. Wyrwicz12, E. Schott13, S.P. Choo14, R.K. Kelley15, D. Begic16, G. Chen17, J. Neely18, J. Anderson19, B. Sangro20 1 Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China, 2 Department of Cancer Control and Population Health, NCC-GCSP, Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea, 3Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 4Department of Internal Medicine, National Taiwan University Hospital Cancer Center, Taipei, Taiwan, 5Service d’He´patologie, Centre Hospitalo-Universitaire Claude Huriez, Lille, France, 6Medical and Digestive Oncology, Centre Eugene - Marquis, Rennes, France, 7Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan, 8Internal Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea, 9Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, 10Hepatology Unit, Hoˆpital de la Croix-Rousse, Lyon, France, 11 Hepatogastroenterology, Assistance Publique Hoˆpitaux de Paris, Hoˆpital Pitie´Salpe´trie`re – Universite´ Pierre et Marie Curie, Paris, France, 12Department of Gastrointestinal Cancer, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, 13Internal Medicine II - Gastroenterology, Hepatology and Diabetology, Helios Klinikum Emil von Behring GmbH, Klinik fu¨r Innere Medizin II, Berlin, Germany, 14Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 15Medicine, University of California San Francisco Parnassus Campus, San Francisco, CA, USA, 16Global Clinical Research/Immuno-Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 17GBS - Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 18 Immuno-Oncology Biomarker Lead for HCC & SCCHN, Bristol-Myers Squibb, Princeton, NJ, USA, 19Immuno-Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 20 Hepatology, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain Background: SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to prolong survival and improve tolerability. This phase III study compared clinical efficacy and safety of NIVO with SOR as 1L therapy in pts with aHCC. Methods: Systemic therapy–naive pts aged 18 years with aHCC were randomized 1:1 to NIVO (240 mg IV Q2W) or SOR (400 mg oral BID). Primary endpoint was overall survival (OS). Additional endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review per RECIST v1.1, efficacy by tumor programmed death ligand 1 (PD-L1) expression, and safety. Results: 743 pts with aHCC were randomized to NIVO (n ¼ 371) or SOR (n ¼ 372) with minimum follow-up of 22.8 months at data cutoff. OS did not meet the predefined threshold of statistical significance (HR 0.84, P ¼ 0.0419). Median OS (mOS) was 16.4 mo for NIVO and 14.7 mo for SOR (HR 0.85 [95% CI: 0.72–1.02]; P ¼ 0.0752). Clinical benefit was observed across predefined subgroups, including hepatitis infection status, presence of vascular invasion and/or extrahepatic spread, and region (Asia vs non-Asia). ORR was 15% for NIVO (14 pts with complete response [CR]) and 7% for SOR (5 pts with CR; Table). Grade 3/4 treatment-related adverse events were reported in 81 pts (22%) in the NIVO arm and 179 pts (49%) in the SOR arm and led to discontinuation in 16 (4%) and 29 (8%) pts, respectively. No new safety signals were observed with NIVO. 140 pts (38%) in the NIVO arm and 170 pts (46%) in the SOR arm received subsequent therapy. Additional OS analyses and patient-reported outcomes will be presented to support the benefit of NIVO.
v874 | Gastrointestinal tumours, non-colorectal
Table: LBA38_PR Efficacy results NIVO n ¼ 371 Median OS (95% CI), mo 16.4 (13.9–18.4) 12-mo OS rate, % (95% CI) 59.7 (54.4–64.6) 24-mo OS rate, % (95% CI) 36.8 (31.8–41.8) Median PFS, mo (95% CI) 3.7 (3.1–3.9) ORR, n (%) 57 (15) BOR, n (%) Complete response 14 (4) Partial response 43 (12) ORR by baseline tumor PD-L1 expression, n/n (%) PD-L1 1% 20/71 (28) PD-L1 <1% 36/295 (12)
SOR n ¼ 372 14.7 (11.9–17.2) 55.1 (49.8–60.1) 33.1 (28.3–38.0) 3.8 (3.7–4.5) 26 (7) 5 (1) 21 (6) 6/64 (9) 20/300 (7)
Conclusions: Though the primary endpoint of OS did not achieve statistical significance vs SOR, NIVO showed clinically meaningful improvements in OS, ORR, and CR rate as 1L treatment for aHCC. NIVO demonstrated a favorable safety profile consistent with previous reports. Clinical trial identification: NCT02576509. Editorial acknowledgement: Writing and editorial assistance was provided by Andrea L. Hammons of Parexel International (Waltham, MA, USA) and funded by BristolMyers Squibb. Legal entity responsible for the study: Bristol-Myers Squibb. Funding: Bristol-Myers Squibb. Disclosure: T. Yau: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb. R.S. Finn: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Honoraria (self), Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Roche/ Genentech. A. Cheng: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Merck Sharp Dohme; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin; Speaker Bureau / Expert testimony: Amgen Taiwan; Advisory / Consultancy: Ispen; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. P. Mathurin: Honoraria (self), Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: Bayer Healthcare ; Honoraria (self), Speaker Bureau / Expert testimony: AbbVie; Honoraria (self), Speaker Bureau / Expert testimony: Gilead; Honoraria (self), Speaker Bureau / Expert testimony: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi. J. Edeline: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony: IPSEN; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Travel / Accommodation / Expenses: Amgen. M. Kudo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Ono; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medico’s Hirata; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): EA Pharma; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Gilead. J.J. Harding: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Speaker Bureau / Expert testimony: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony: Elly Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: CytomX; Honoraria (self), Speaker Bureau / Expert testimony: QED. P. Merle: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: AstraZeneca. O. Rosmorduc: Honoraria (self): Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Sirtex; Honoraria (self): Eisai. L. Wyrwicz: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Beigene; Research grant / Funding (self): Eisai. E. Schott: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bayer. S.P. Choo: Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy: Sirtex; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen. R.K. Kelley: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, IDMC membership: Genentech/Roche; Research grant / Funding (institution): Merck; Research grant / Funding
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Annals of Oncology
Annals of Oncology (institution): Regeneron; Research grant / Funding (institution): AstraZeneca. D. Begic: Full / Parttime employment: Bristol-Myers Squibb. J. Neely: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. B. Sangro: Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: BTG; Advisory / Consultancy: H3 Biomedicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sirtex Medical; Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Terumo. All other authors have declared no conflicts of interest.
Randomised efficacy and safety results for atezolizumab (Atezo) 1 bevacizumab (Bev) in patients (pts) with previously untreated, unresectable hepatocellular carcinoma (HCC)
M. Lee1, B-Y. Ryoo2, C-H. Hsu3, K. Numata4, S. Stein5, W. Verret6, S. Hack6, J. Spahn6, B. Liu7, H. Abdullah8, R. He9, K-H. Lee10 1 UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan, 4Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan, 5 Medical 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, 8Safety Science Oncology, Genentech, Inc., South San Francisco, CA, USA, 9Department of Medicine, Georgetown University Medical Center, Washington, DC, USA, 10Internal Medicine, Seoul National University Hospital, 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, bev 15 mg/kg IV q3w until unacceptable toxicity or loss of clinical benefit. Arm A pts received atezo þ bev. Primary endpoints
Volume 30 | Supplement 5 | October 2019
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 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% 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: Medical writing assistance was provided by Steffen Biechele, 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: M. Lee: Research grant / Funding (self): Amgen; Research grant / Funding (self): BristolMyers 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.
doi:10.1093/annonc/mdz394 | v875
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