Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (2019)
17 slides from Roche's technical presentation, 2019
Slide 1: Atezolizumab + bevacizumab vs sorafenib in unresectable hepatocellular carcinoma: IMbrave150
Atezolizumab + bevacizumab vs sorafenib in patients with unresectable hepatocellular carcinoma: Phase 3 results from IMbrave150 Ann-Lii Cheng,1 Shukui Qin,2 Masafumi Ikeda,3 Peter R. Galle,4 Michel Ducreux,5 Andrew X. Zhu,6 Tae-You Kim,7 Masatoshi Kudo,8 Valeriy Breder,9 Philippe Merle,10 Ahmed Kase
Slide 2: Disclosures
Disclosures • Dr Cheng has received honoraria from AstraZeneca, Bayer Yakuhin, Eisai, Genentech/Roche and Lilly and consulting/advisory fees from AstraZeneca, Bayer Schering Pharma, BeiGene, Bristol-Myers Squibb, CSR Pharma Group, Eisai, Genentech/Roche, MSD, Novartis and Ono Pharmaceutical • F. Hof
Slide 3: Background
Background • Multikinase inhibitors sorafenib and lenvatinib are the preferred first-line systemic treatments for unresectable hepatocellular carcinoma (HCC)1-7 • While these agents have had modest effects on overall survival, they are both associated with considerable side effects • With sorafenib,
Slide 4: IMbrave150 study design
IMbrave150 study design Atezolizumab Stratification 1200 mg IV q3w • Region (Asia, excluding + Key eligibility Japana/rest of world) bevacizumab • Locally advanced 15 mg/kg q3w Until loss of or metastatic • ECOG PS (0/1) clinical and/or benefit or Survival • Macrovascular invasion R N = 501b un- fol
Slide 5: IMbrave150 statistical testing hierarchy
IMbrave150 statistical testing hierarchy Atezo + Bev vs Sorafenib 2-sided α = 0.05 OS PFS IA1 α = 0.0033 α = 0.002 based on 161 events observed IRF-ORR per RECIST 1.1 α = 0.002 Primary endpoint IRF-ORR per HCC mRECIST Secondary α = 0.002 endpoint IA, interim analysis. Alpha recycling per graphical m
Slide 6: IMbrave150 baseline characteristics (ITT)
IMbrave150 baseline characteristics (ITT) Characteristic Atezo + Bev Sorafenib (n = 336) (n = 165) Median age (range), years 64 (26-88) 66 (33-87) Sex, male, n (%) 277 (82) 137 (83) Region, n (%) Asia (excluding Japana) 133 (40) 68 (41) Rest of world 203 (60) 97 (59) ECOG PS 1, n (%) 127 (38) 62 (38
Slide 7: OS: co-primary endpoint
OS: co-primary endpoint Median OS (95% CI), moa Atezo + Bev NE Sorafenib 13.2 (10.4, NE) 6-mo OS rate: 85% HR, 0.58 (95% CI: 0.42, 0.79)b P = 0.0006b,c 6-mo OS rate: 72% mOS: NE mOS: 13.2 mo NE, not estimable. a 96 patients (29%) in the Atezo + Bev arm vs 65 (39%) in the sorafenib arm had an event.
Slide 8: Confirmed PFS: co-primary endpoint
Confirmed PFSa: co-primary endpoint Median PFS (95% CI), mob Atezo + Bev 6.8 (5.7, 8.3) 6-mo PFS rate: 55% Sorafenib 4.3 (4.0, 5.6) 6-mo PFS rate: 37% HR, 0.59 (95% CI: 0.47, 0.76)c,d P < 0.0001d mPFS: 4.3 mo mPFS: 6.8 mo a Assessed by IRF per RECIST 1.1. b 197 patients (59%) in the Atezo + Bev arm
Slide 9: OS subgroups
OS subgroups Atezo + Bev Sorafenib mOS, mo mOS, mo Characteristic (n) (n = 336) (n = 165) HR (95% CI)a All patients (501) NE 13.2 0.58 (0.42, 0.79) Asia (excluding Japanb) (201) NE 13.1 0.53 (0.32, 0.87) Rest of world (300) NE 13.2 0.65 (0.44, 0.98) ECOG PS 0 (312) NE 13.9 0.67 (0.43, 1.06) ECOG PS
Slide 10: PFS subgroups
PFS subgroups Atezo + Bev Sorafenib mPFS, mo mPFS, mo Characteristic (n) (n = 336) (n = 165) HR (95% CI)a All patients (501) 6.8 4.3 0.59 (0.47, 0.76) Asia (excluding Japanb) (201) 7.7 2.8 0.46 (0.31, 0.67) Rest of world (300) 6.7 4.9 0.70 (0.52, 0.96) ECOG PS 0 (312) 7.9 4.8 0.57 (0.42, 0.78) ECOG
Slide 11: Response rate and duration of response
Response rate and duration of response IRF RECIST 1.1 IRF HCC mRECIST Atezo + Bev Sorafenib Atezo + Bev Sorafenib (n = 326) (n = 159) (n = 325)a (n = 158) Confirmed ORR, n (%) 89 (27) 19 (12) 108 (33) 21 (13) (95% CI) (23, 33) (7, 18) (28, 39) (8, 20) CR 18 (6) 0 33 (10) 3 (2) PR 71 (22) 19 (12) 75
Slide 12: Safety summary
Safety summarya Characteristic Atezo + Bev Sorafenib (n = 329) (n = 156) Treatment duration, median, mo Atezo = 7.4; Bev = 6.9 2.8 All-Grade AEs, any cause, n (%) 323 (98) 154 (99) Treatment-related all-Grade AEs 276 (84) 147 (94) Grade 3-4 AE , n (%)b 186 (57) 86 (55) Treatment-related Grade 3-4 AE
Slide 13: Safety
Safetya ≥ 10% frequency of AEs in either arm and > 5% difference between arms Atezo + Bev Sorafenib Diarrhoea PPE Decreased appetite Hypertension Abdominal pain Alopecia Asthenia Pyrexia ALT increased Proteinuria All-Grade AEs All-Grade AEs Infusion-related reaction Grade 3-4 AEs Grade 3-4 AEs 60% 5
Slide 14: Patient-reported outcomes
Patient-reported outcomesa Quality of life Median TTD (95% CI), mob • Atezolizumab + bevacizumab Atezo + Bev 11.2 (6.0, NE) ,% delayed the time to deterioration Sorafenib 3.6 (3.0, 7.0) of patient-reported quality of life HR, 0.63 (95% CI: 0.46, 0.85) compared with sorafenib EORTC QLQ-C30, European
Slide 15: IMbrave150 conclusions
IMbrave150 conclusions • IMbrave150 demonstrated statistically significant and clinically meaningful improvement with atezolizumab + bevacizumab over sorafenib for OS and IRF-assessed PFS per RECIST 1.1 • OS HR, 0.58 (95% CI: 0.42, 0.79); P = 0.0006 Co-primary endpoints • IRF-PFS HR, 0.59 (95% CI: 0
Slide 16: Acknowledgements
Acknowledgements • The patients and their families • The investigators and clinical study sites • This study is sponsored by F. Hoffmann-La Roche, Ltd • Medical writing assistance for this oral presentation was provided by Paige S. Davies, PhD, of Health Interactions and funded by F. Hoffmann-La Roc
Slide 17: Investigator list
Investigator list R. Anty Y. Chao P. Gold H. Koga S. Qin W. Wang T. Aramaki M. Chen K. Gu M. Kudo Z. Ren H. Wege R. Asghari X. Chen S. Gu M. Kundranda P. Ross M. Wieczorek-Rutkowska J. Asselah A.-L. Cheng Y. Guo D. Li P. Rozanowski M. Wörns E. Assenat Y. Cheng A. Hagihara W. Li B.-Y. Ryoo J. Wu J.-H