Dataset Information

Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study.

ABSTRACT:

Introduction

Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported.

Methods

IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population.

Results

Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25-0.76) and for PFS was 0.60 (95% CI, 0.40-0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2-8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6-4.8) with sorafenib. Grade 3-4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3-4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent.

Conclusion

Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

SUBMITTER: Qin S

PROVIDER: S-EPMC8339481 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe efficacy of systemic first-line treatments in older adults with unresectable hepatocellular carcinoma (HCC) has not been well-studied. We compared the safety and efficacy of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment in younger versus older patients with unresectable HCC.MethodsThis global, phase 3, open-label, randomized clinical trial (IMbrave150) recruited patients aged ≥18 years with locally advanced metastatic or unresectable HCC, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and Child-Pugh class A liver function who had not previously received systemic therapy for liver cancer. Patients received either 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily until loss of clinical benefit or unacceptable toxicity. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the incidence of adverse events and time to deterioration of patient-reported outcomes (PROs). This subgroup analysis evaluated safety and efficacy endpoints in patients <65 years, ≥65 to <75 years, and ≥75 years.ResultsOf 501 patients, 165 patients were randomized to sorafenib and 336 were randomized to atezolizumab plus bevacizumab (175 patients <65 years; 106 patients ≥65 to <75 years; 55 patients ≥75 years). Across all age groups, patients receiving atezolizumab plus bevacizumab had longer median OS (<65: 18.0 vs. 12.2 months [HR, 0.57; 95% CI: 0.40-0.82]; ≥65 to <75: 19.4 vs. 14.9 months [HR, 0.80; 95% CI: 0.52-1.23]; ≥75: 24.0 vs. 18.0 months [HR, 0.72, 95% CI: 0.37-1.41]) and PFS than those receiving sorafenib. Time to deterioration for multiple PROs was delayed for patients receiving atezolizumab plus bevacizumab, including older adults. There were no clinically meaningful differences in toxicity between age groups.ConclusionAtezolizumab plus bevacizumab is safe and effective in adults <65, ≥65 to <75, and ≥75. Treatment was well-tolerated even in elderly patients.

Project description:ImportanceAtezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed.ObjectiveTo evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective.Design, setting, and participantsThis economic evaluation was performed from June through September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features.Main outcomes and measuresHealth care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness.ResultsIn the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs) and with an incremental cost of $156 210 per patient compared with sorafenib. The ICER was $322 500 per QALY (5th to 95th percentile, $149 364-$683 744 per QALY), with 0.6% and 5.1% chance of being cost-effective at willingness-to-pay thresholds of $100 000 and $150 000 per QALY, respectively. The ICER never decreased below $150 000 per QALY in the 1-way sensitivity analyses. To achieve more favorable cost-effectiveness under the thresholds of $150 000 to $100 000 per QALY, the prices of atezolizumab and bevacizumab would need to be reduced by 37% to 47%.Conclusions and relevanceIn this economic evaluation, atezolizumab plus bevacizumab was associated with clinical benefit but was not cost-effective compared with sorafenib for first-line treatment of unresectable or metastatic hepatocellular carcinoma from a US payer perspective. A substantial reduction in price for atezolizumab plus bevacizumab would be needed to achieve favorable cost-effectiveness for this new therapy.

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