In an analysis from the phase III IMbrave150 trial reported in The Lancet Oncology, Peter R. Galle, MD, and colleagues found that patients receiving atezolizumab plus bevacizumab had better patient-reported outcomes vs those receiving sorafenib for advanced unresectable or metastatic hepatocellular carcinoma not previously treated with systemic therapy.
As previously reported, the trial showed improved overall survival and improved progression-free survival on independent review with atezolizumab/bevacizumab vs sorafenib, and supported the May 2020 approval of atezolizumab/bevacizumab for treatment of patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.
Peter R. Galle, MD
Study Details
In the open-label trial, 501 patients were randomly assigned 2:1 to receive atezolizumab at 1,200 mg plus bevacizumab at 1,200 mg intravenously once every 3 weeks (n = 336) or oral sorafenib at 400 mg twice daily (n =165) until loss of clinical benefit or unacceptable toxicity. Patient-reported quality of life, functioning, and disease symptoms were assessed by the EORTC quality-of-life questionnaire for cancer (QLQ-C30) and quality-of-life questionnaire for hepatocellular carcinoma (QLQ-HCC18).
Patients were to complete questionnaires at the clinic site on day 1 of treatment cycle 1 (baseline) and on day 1 of every 3-week cycle thereafter, up to and including the treatment discontinuation visit. Time to confirmed deterioration of patient-reported outcomes was analyzed in the intention-to-treat population; all other analyses were performed in the patient-reported outcomes–evaluable population, consisting of patients with a baseline patient-reported outcomes assessment and at least one postbaseline assessment.
Key Findings
At data cutoff (August 2019), the median follow-up was 8.6 months (interquartile range = 6.2–10.8 months). A total of 309 patients in the atezolizumab/ bevacizumab group and 145 in the sorafenib group were included in the patient-reported outcomes–evaluable population.
QLQ-C30 completion rates were ≥ 90% for 23 of 24 treatment cycles in both groups. QLQ-HCC18 completion rates were ≥ 90% for 20 of 24 cycles in the atezolizumab/bevacizumab group and 21 of 24 cycles in the sorafenib group.
On all four QLQ-C30 symptom scales prespecified for analysis, patients in the atezolizumab/bevacizumab group vs the sorafenib group had significantly reduced risk of deterioration: hazard ratios (HRs) were 0.57 (95% confidence interval [CI] = 0.40–0.81) for appetite loss, 0.23 (95% CI = 0.16–0.34) for diarrhea, 0.61 (95% CI = 0.46–0.81) for fatigue, and 0.46 (95% CI = 0.34–0.62) for pain.
Among the three QLQ-HCC18 disease-specific symptom scales prespecified for analysis, patients in the atezolizumab/bevacizumab group had a significantly reduced risk for fatigue (HR = 0.60, 95% CI = 0.45–0.80) and pain (HR = 0.65, 95% CI = 0.46–0.92) but not for jaundice (HR = 0.76, 95% CI = 0.55–1.07).
Risk of deterioration on other QLQ-C30 scales was significantly lower in the atezolizumab/bevacizumab group for function-emotional, function-social, function-cognitive, nausea and vomiting, dyspnea, and insomnia, but not for constipation or financial difficulties. Risk of deterioration on other QLQ-HCC18 scales was significantly lower in the atezolizumab/bevacizumab group for abdominal swelling, body image, and nutrition, but not for fever or sex life.
At day 1 of treatment cycle 5 in the patient-reported outcomes–evaluable population, beyond which attrition in the sorafenib group exceeded 50%, mean QLQ-C30 score changes from baseline in the atezolizumab/bevacizumab vs sorafenib groups were: –3.29 vs –5.83 for quality of life, –4.02 vs –9.76 for role functioning, and –3.77 vs –7.60 for physical functioning.
For QLQ-C30 quality of life, proportions of patients in the atezolizumab/bevacizumab vs sorafenib patient-reported outcomes–evaluable groups with clinically meaningful improvement (increase of ≥ 10 points), stability, and clinically meaningful deterioration (decrease of ≥ 10 points) on day 1 of each cycle were: 15%, 57%, and 29% vs 11%, 48%, and 41% at cycle 2; 14%, 57%, and 30% vs 9%, 49%, and 42% at cycle 3; 13%, 60%, and 27% vs 8%, 55%, and 38% at cycle 4; and 13%, 59%, and 28% vs 4%, 64%, and 31% at cycle 5.
The investigators concluded, “Prespecified analyses of patient-reported outcomes data showed clinically meaningful benefits in terms of patient-reported quality of life, functioning, and disease symptoms with atezolizumab plus bevacizumab compared with sorafenib, strengthening the combination therapy’s positive benefit-risk profile vs that of sorafenib in patients with unresectable hepatocellular carcinoma.”
Dr. Galle, of the Department of Internal Medicine, University Medical Center Mainz, Germany, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit thelancet.com.
