For the first-line treatment of advanced hepatocellular carcinoma, atezolizumab plus bevacizumab provided a significant overall survival benefit in the pivotal IMbrave150 trial. New findings from a prespecified analysis also showed numerous benefits for the doublet in terms of quality of life, IMbrave150 investigators reported at the 2020 Gastrointestinal Cancers Symposium.1
Peter R. Galle, MD
“Deteriorations in quality of life, role functioning, physical functioning, and key symptoms were all delayed with atezolizumab/bevacizumab, and they occurred less often with the combination than with sorafenib,” reported Peter R. Galle, MD, of the University Medical Center Mainz and President of the German Association for the Study of the Liver. “Quality of life matters to patients with cancer, particularly in a palliative setting, when there is a limited lifespan. For that reason, the voice of the patient needs to be heard,” he continued. “In hepatocellular carcinoma, it might even be more complex because this patient is attacked not just by a tumor, but also by poor liver function.”
IMbrave150: Survival Benefits
IMbrave150 included 501 patients with unresectable advanced or metastatic hepatocellular carcinoma. They were randomly assigned to atezolizumab/bevacizumab or sorafenib and treated until loss of efficacy or unacceptable toxicity. The efficacy data, presented at the European Society for Medical Oncology (ESMO) Asia Congress 2019, showed that overall survival was not reached with atezolizumab/bevacizumab and was 13.2 months with sorafenib (hazard ratio [HR] = 0.58; P = .0006).2 Likewise, progression-free survival was significantly improved to 6.8 months, vs 4.3 months, respectively (HR = 0.59; P < .0001). “These curves separated from the first assessment and remained separated throughout,” noted Dr. Galle.
“Quality of life matters to patients with cancer, particularly in a palliative setting when there is a limited lifespan. For that reason, the voice of the patient needs to be heard.”— Peter R. Galle, MD
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For grade 3 or 4 adverse events, sorafenib-treated patients had more diarrhea and hand-foot reactions, decreased appetite, alopecia, and asthenia. As for patients treated with atezolizumab/bevacizumab, there were fewer symptomatic toxicities—hypertension, proteinuria, hepatitis, and pyrexia.
Less Deterioration in Quality of Life
Dr. Galle presented the prespecified endpoint of time to deterioration of quality of life, physical functioning, and role functioning by the European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 addresses these issues on a 100-point scale, with a drop of at least 10 points considered to be clinically meaningful. Patients were queried about things such as work, pursuit of hobbies, ability to walk a distance, and symptoms. The two arms were well balanced, and patients generally began treatment at a “relatively high” level of functioning, said Dr. Galle, with baseline scores of about 70 on a 100-point scale.
Analysis of patient-reported outcomes showed that fewer patients treated with atezolizumab/bevacizumab experienced deterioration in quality of life; for those who did experience some deterioration in quality of life, it had a later onset. “The difference was quite remarkable,” Dr. Galle observed. The median time to quality-of-life deterioration was 3.6 months with sorafenib and 11.2 months with atezolizumab/bevacizumab (HR = 0.63). Clinically meaningful declines in quality of life were more common in all cycles among the sorafenib group. Such declines were reported by approximately 46% to 44% of those in the sorafenib cohort (depending on the cycle), vs approximately 30% of those in the experimental group.
“In any given cycle, atezolizumab/bevacizumab was favored, with a lower percentage of patients showing deterioration in quality of life,” stated Dr. Galle. Similar findings were made for the time to deterioration in physical functioning and role functioning, with approximately a 5-month difference in each (HR = 0.53 and 0.62, respectively). As for the time to deterioration in symptoms, again, all favored atezolizumab/bevacizumab, including appetite loss, diarrhea, fatigue, jaundice, and pain.
“IMbrave150 demonstrated statistically significant and clinically meaningful improvements in overall and progression-free survival by independent review at a level not seen before compared with sorafenib. The data on patient-reported outcomes also demonstrated clinically meaningful benefits in key aspects of patients’ experiences,” Dr. Galle concluded. “These patient-reported outcomes—the patient’s voice—further support the positive benefit/risk profile of atezolizumab and bevacizumab and complement the efficacy data in these patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.
DISCLOSURE: The IMbrave150 study was supported by Hoffmann-La Roche. Dr. Galle has received consulting or advisory fees from Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Sirtex, Lilly, Blueprint, AdaptImmune, Eisai, Roche, and Ipsen and has received grant funding from Bayer.
1. Galle PR, Finn RS, Qin S, et al: Patient-reported outcomes from the phase III IMbrave150 trial of atezolizumab plus bevacizumab vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma. 2020 Gastrointestinal Cancers Symposium. Abstract 476. Presented January 24, 2020.
2. Cheng A, Qin S, Ikeda M, et al: IMbrave150: Efficacy and safety results from a phase III study evaluating atezolizumab + bevacizumab vs sorafenib as first treatment for patients with unresectable hepatocellular carcinoma. 2019 ESMO Asia Congress. Abstract LBA3. Presented November 23, 2019.
The invited discussant of the IMbrave150 trial, A. Craig Lockhart, MD, Professor of Medicine, University of Miami Sylvester Comprehensive Cancer Center, applauded the study for making patient-reported outcomes a prespecified endpoint and described the value of having this information. “The U.S....