IMbrave150 Trial of Atezolizumab + Bevacizumab vs Sorafenib as - - PowerPoint PPT Presentation

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IMbrave150 Trial of Atezolizumab + Bevacizumab vs Sorafenib as - - PowerPoint PPT Presentation

Dec 25, 2023 1.42k likes •1.68k views

Patient-Reported Outcomes From the Phase 3 IMbrave150 Trial of Atezolizumab + Bevacizumab vs Sorafenib as First-Line Treatment for Patients With Unresectable Hepatocellular Carcinoma Peter R. Galle, 1 Richard S. Finn, 2 Shukui Qin, 3 Masafumi

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Dr Galle PROs in IMbrave150 https://bit.ly/37HcR1p

Patient-Reported Outcomes From the Phase 3 IMbrave150 Trial of Atezolizumab + Bevacizumab vs Sorafenib as First-Line Treatment for Patients With Unresectable Hepatocellular Carcinoma

Peter R. Galle,1 Richard S. Finn,2 Shukui Qin,3 Masafumi Ikeda,4 Andrew X. Zhu,5 Tae-You Kim,6 Masatoshi Kudo,7 Valeriy Breder,8 Philippe Merle,9 Ahmed Kaseb,10 Daneng Li,11 Sohail Mulla,12 Wendy Verret,13 Derek- Zhen Xu,14 Sairy Hernandez,13 Beiying Ding,13 Juan Liu,14 Chen Huang,14 Ho Yeong Lim,15 Ann-Lii Cheng,16 Michel Ducreux17

1University Medical Center Mainz, Mainz, Germany; 2Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA,

Los Angeles, CA; 3People’s Liberation Army Cancer Center, Nanjing, People’s Republic of China; 4National Cancer Center Hospital East, Kashiwa, Japan; 5Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, MA; 6Seoul National University College of Medicine, Seoul, Korea; 7Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan; 8Russian Cancer Research Center by NN Blikhin, Moscow, Russia; 9Hospital La Croix-Rousse, Lyon, France; 10Department of Hemopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; 11Department of Medical Oncology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA; 12Hoffmann-La Roche Limited, Mississauga, ON, Canada; 13Genentech, Inc., South San Francisco, CA; 14Roche Product Development, Shanghai, People’s Republic of China; 15Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 16National Taiwan University Cancer Center, Taipei, Taiwan; 17Gustave Roussy, Villejuif, France

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Disclosures

  • Dr Galle reports the following disclosures: grant from Bayer;

consulting/advisory fees from Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Sirtex, Merck, Lilly, Blueprint, Adaptimmune, Eisai, Roche and Ipsen

  • F. Hoffmann-La Roche, Ltd, sponsored the study and was involved in

study design, analysis and interpretation of results and development of this report

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IMbrave150 Study Design

EORTC, European Organisation for Research and Treatment of Cancer; IRF, independent review facility; mRECIST, modified RECIST; TTD, time to deterioration.

a Japan is included in rest of world. b Time from randomization to first decrease from baseline of ≥ 10 points maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. c Time from randomization to the

first increase from baseline of ≥ 10 points in the symptom scales maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks.

(Open label) Survival follow- up Until loss

  • f clinical

benefit

  • r un-

acceptable toxicity Sorafenib 400 mg bid Atezolizumab 1200 mg IV q3w + bevacizumab 15 mg/kg q3w Stratification criteria

  • Region (Asia, excluding Japana/

rest of world)

  • ECOG PS (0/1)
  • Macrovascular invasion and/or

extrahepatic spread (presence/absence)

  • Baseline AFP

(< 400/≥ 400 ng/mL) Key eligibility

  • Locally advanced
  • r metastatic

and/or unresectable HCC

  • No prior systemic

therapy (N = 501)

R 2:1

Co-primary endpoints

  • OS
  • IRF-assessed PFS

per RECIST 1.1 Secondary endpoints include

  • IRF-assessed ORR per RECIST 1.1 and

HCC mRECIST

  • PROs: TTDb of QOL, physical and role

functioning (EORTC QLQ-C30) Exploratory PRO endpoints

  • TTDc of symptoms (EORTC QLQ-HCC18)
  • Patients (%) with clinically meaningful

deterioration in QOL, physical and role functioning

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IMbrave150 Co-Primary Endpoints: OS and PFS1

OS

Atezo + Bev Sorafenib Median (95% CI), mo NE 13.2 (10.4, NE) HR P value 0.58 (95% CI: 0.42, 0.79)a 0.0006b

NE, not estimable. Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a HR and P value were from Cox model and log-rank test and were stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS. b The 2-sided P value boundary based on 161 events is 0.0033. c The 2-sided P value boundary is 0.002. 1. Cheng A-L, et al. Ann Oncol. 2019;30(suppl 9) [abstract LBA3].

PFS (IRF assessed RECIST 1.1)

Atezo + Bev Sorafenib Median (95% CI), mo 6.8 (5.7, 8.3) 4.3 (4.0, 5.6) HR P value 0.59 (95% CI: 0.47, 0.76)a < 0.0001c

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Safety1,a

≥ 10% frequency of AEs in either arm and > 5% difference between arms

a Safety analysis population. 1. Cheng A-L, et al. Ann Oncol. 2019;30(suppl 9) [abstract LBA3].

40% 20% 20% 10% 60% 60% 40% 50% 30% 50% 10% 30%

Atezo + Bev (n = 329)

Diarrhea Hypertension Palmar-plantar erythrodysesthesia Pyrexia ALT increased Proteinuria Alopecia Decreased appetite Asthenia Abdominal pain Infusion-related reaction

All-Grade AEs All-Grade AEs Grade 3-4 AEs Grade 3-4 AEs

Sorafenib (n = 156)

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Assessment of PROs in IMbrave150

  • PROs evaluated key aspects of the patient experience while receiving treatment with

atezolizumab + bevacizumab vs sorafenib in patients with HCC

  • Patients completed the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires every

3 weeks while on treatment until treatment discontinuation or progression and every 3 months thereafter for 1 year

  • Questionnaire completion rates were high (≥ 92%) during most of the treatment period

Symptoms: fatigue, pain, appetite loss, diarrhea, jaundice Functioning: physical, role Quality of Life

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Time to Deterioration in Quality of Life1,a

Baseline QOL scoreb Mean (SD)

Atezo + Bev 68.79 (21.20) Sorafenib 71.04 (21.07) Better QOL

Min Max 100

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the global health status/QOL scale of EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145). c HR from Cox model and stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS. 1. Cheng A-L, et al. Ann

  • Oncol. 2019;30(suppl 9) [abstract LBA3].
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Time to Deterioration in Quality of Life1,a

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the global health status/QOL scale of EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145). c HR from Cox model and stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS. 1. Cheng A-L, et al. Ann

  • Oncol. 2019;30(suppl 9) [abstract LBA3].

Deterioration-free rate (%)

Quality of life (ITT)

Atezo + Bev (n = 336) Sorafenib (n = 165) Median TTD, mo (95% CI) 11.2 (6.0, NE) 3.6 (3.0, 7.0) HR 0.63 (95% CI: 0.46, 0.85)c

Baseline QOL scoreb Mean (SD)

Atezo + Bev 68.79 (21.20) Sorafenib 71.04 (21.07) Better QOL

Min Max 100

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29.9% 31.5% 30.2% 29.6% 44.2% 43.0% 41.4% 35.7%

20 40 60 80 100

Cycle 2 Cycle 3 Cycle 4 Cycle 5

Atezolizumab + Bevacizumab Sorafenib

Clinically Meaningful Deterioration: Quality of Lifea

  • A change in QOL from baseline of ≥ 10 points has been perceived by patients to be clinically

meaningful1

Day 1 of: Clinically Meaningful Deterioration Compared With Baseline (%)

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145).

  • 1. Osoba D, et al. J Clin Oncol. 1998;16(1):139-144.

(n = 253) (n = 276) (n = 268) (n = 298) (n = 129) (n = 100) (n = 87) (n = 70)

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Min Max 100

Time to Deterioration in Physical Functioninga

Atezo + Bev 84.82 (17.75) Sorafenib 85.73 (16.32)

Baseline Physical Functioning Scoreb Mean (SD)

Better functioning

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the physical functioning scale of the EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145).

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Time to Deterioration in Physical Functioninga

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the physical functioning scale of the EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145). c HR from Cox model and stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS.

Physical functioning (ITT)

Atezo + Bev (n = 336) Sorafenib (n = 165) Median TTD (95% CI), mo 13.1 (9.7, NE) 4.9 (3.5, 6.2) HR 0.53 (95% CI: 0.39, 0.73)c Deterioration-free rate (%)

Baseline Physical Functioning Scoreb Mean (SD)

Min Max 100

Atezo + Bev 84.82 (17.75) Sorafenib 85.73 (16.32) Better functioning

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24.2% 21.3% 22.3% 22.9% 39.5% 37.0% 38.6% 31.4% 20 40 60 80 100

Cycle 2 Cycle 3 Cycle 4 Cycle 5

Atezolizumab + Bevacizumab Sorafenib

Clinically Meaningful Deterioration: Physical Functioninga

Day 1 of:

(n = 253) (n = 277) (n = 269) (n = 297) (n = 129) (n = 100) (n = 88) (n = 70)

  • A change in physical functioning from baseline of ≥ 10 points has been perceived by patients to be

clinically meaningful1

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145).

  • 1. Osoba D, et al. J Clin Oncol. 1998;16(1):139-144.

Clinically Meaningful Deterioration Compared With Baseline (%)

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Min Max 100

Time to Deterioration in Role Functioninga

Atezo + Bev 85.75 (21.60) Sorafenib 85.01 (23.03)

Baseline Role Functioning Scoreb Mean (SD)

Better functioning

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the role functioning scale

  • f the EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo +

bev, n = 309; sorafenib, n = 145).

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Dr Galle PROs in IMbrave150 https://bit.ly/37HcR1p

Time to Deterioration in Role Functioninga

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Pre-specified secondary endpoint that was not formally tested. TTD was defined as the time from randomization to first decrease from baseline of ≥ 10 points in the role functioning scale

  • f the EORTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev,

n = 309; sorafenib, n = 145). c HR from Cox model and stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS.

Role functioning (ITT)

Atezo + Bev (n = 336) Sorafenib (n = 165) Median TTD (95% CI), mo 9.1 (6.5, NE) 3.6 (2.2, 6.0) HR 0.62 (95% CI: 0.46, 0.84)c

Baseline Role Functioning Scoreb Mean (SD)

Deterioration-free rate (%)

Min Max 100

Atezo + Bev 85.75 (21.60) Sorafenib 85.01 (23.03) Better functioning

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29.3% 29.6% 27.1% 28.1% 41.1% 42.0% 37.5% 31.4% 20 40 60 80 100

Cycle 2 Cycle 3 Cycle 4 Cycle 5

Atezolizumab + Bevacizumab Sorafenib

Clinically Meaningful Deterioration: Role Functioninga

Day 1 of:

(n = 253) (n = 277) (n = 269) (n = 297) (n = 129) (n = 100) (n = 88) (n = 70)

Clinically Meaningful Deterioration Compared With Baseline (%)

  • A change in role functioning from baseline of ≥ 10 points has been perceived by patients to be

clinically meaningful1

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a In the PRO-evaluable population, defined as patients who had a baseline and ≥ 1 other PRO assessment (atezo + bev, n = 309; sorafenib, n = 145).

  • 1. Osoba D, et al. J Clin Oncol. 1998;16(1):139-144.
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Time to Deterioration in Symptomsa

Data cutoff, August 29, 2019; median survival follow-up, 8.6 months. a Exploratory endpoint that was not formally tested. TTD was defined as the time from randomization to first increase from baseline of ≥ 10 points in the symptom scales maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. b HR from Cox model and stratified by geographic region (Asia vs rest of world, including Japan), AFP level (< 400 vs ≥ 400 ng/mL) at baseline and MVI and/or EHS (yes vs no) per IxRS.

0.5 1 1.5

Sorafenib better Atezo + Bev better

Scale (questionnaire) Median Time to Event (95% CI), moa HR (95% CI)b Atezo + Bev (n = 336) Sorafenib (n = 165)

Appetite loss NE 7.62 (3.48, NE) 0.57 (0.40, 0.81) Diarrhea NE 4.44 (3.48, 5.59) 0.23 (0.16, 0.34) Fatigue (QLQ-C30) 5.68 (4.30, 7.10) 2.10 (1.45, 4.83) 0.61 (0.46, 0.81) Fatigue (QLQ-HCC18) 5.65 (4.30, 9.03) 2.14 (1.64, 2.83) 0.60 (0.45, 0.80) Jaundice 10.55 (6.93, NE) 6.47 (5.55, NE) 0.76 (0.55, 1.07) Pain (QLQ-C30) 9.72 (7.16, NE) 2.79 (2.14, 4.30) 0.46 (0.34, 0.62) Pain (QLQ-HCC18) NE 9.82 (4.27, NE) 0.65 (0.46, 0.92)

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Conclusions

  • IMbrave150 demonstrated statistically significant and clinically meaningful improvement in OS and

IRF-assessed PFS per RECIST 1.1 with atezolizumab + bevacizumab vs sorafenib

  • High-quality PRO data demonstrated clinically meaningful benefits in key aspects of the patient

experience (QOL, functioning, key symptoms) with atezolizumab + bevacizumab vs sorafenib

  • These PRO data further support the positive benefit:risk profile of atezolizumab + bevacizumab vs

sorafenib in patients with unresectable HCC who have not received prior systemic therapy

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  • The patients and their families
  • Yong Wang for contributions to statistical analyses
  • Participating study investigators and clinical sites
  • This study is sponsored by F. Hoffmann-La Roche, Ltd
  • Medical writing assistance for this presentation was provided by Samantha Santangelo, PhD,
  • f Health Interactions, Inc, and funded by F. Hoffmann-La Roche, Ltd

Acknowledgments

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