Atezolizumab-Bevacizumab Combo Improves Survival and Quality of Life in Unresectable Liver Cancer

The combination of atezolizumab (Tecentriq) immunotherapy plus bevacizumab (Avastin) improves survival as well as significantly delaying deterioration in quality of life compared with the current standard of the targeted therapy sorafenib (Nexavar) in the treatment of patients with unresectable hepatocellular carcinoma (HCC).

Data from the IMbrave150 trial showed a 42% reduction in mortality risk with atezolizumab plus bevacizumab versus sorafenib monotherapy. In addition, the median time to deterioration in quality of life was 11.2 months for the 2-drug combination versus 3.6 months with sorafenib, reported Peter R. Galle, MD, PhD, University Medical Center Mainz, Germany, at the 2020 Gastrointestinal Cancers Symposium.

“Quality of life matters,” said Dr Galle. “It matters to all of us, and in particular in metastatic cancer patients. This is particularly true in a palliative setting, when there is a limited time of life span….The quality of life in the remaining life span is of utmost importance, and for that reason, the voice of the patient needs to be heard. Hepatocellular carcinoma is quite probably even more complex, because this patient is not just attacked by a tumor; he or she is also attacked by a disease [that affects] the liver and function.”

The open-label IMbrave150 trial included 501 patients who were randomized to IV atezolizumab 1200 mg every 3 weeks plus IV bevacizumab 15 mg/kg every 3 weeks, or to sorafenib 400 mg orally twice daily, until loss of clinical benefit or unacceptable toxicity.

Overall survival was 13.2 months for patients randomized to sorafenib and was not reached in the combination arm (hazard ratio, 0.58; P = .0006). Progression-free survival was also superior in the atezolizumab-bevacizumab arm at 6.8 months versus 4.3 months in the sorafenib arm.

As part of the study, patients completed the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires at baseline, every 3 weeks after start of treatment, and every 3 months after treatment discontinuation or disease progression. Questionnaire completion rates were ≥92% in both arms.

Time to quality-of-life deterioration was defined as the time from randomization to first decrease from baseline by ≥10 points. A change in quality of life from baseline by ≥10 points has been perceived by patients to be clinically meaningful.

The median time to deterioration of physical functioning was also delayed with the combination versus sorafenib (13.1 months vs 4.9 months).

Some 39.5% of the patients in the sorafenib arm versus only 24.2% of those in the atezolizumab-bevacizumab arm had clinically meaningful (ie, ≥10 points) deterioration in physical functioning at day 1, cycle 2, an advantage that was maintained through cycle 5 (31.4% of the sorafenib group vs 22.9% of the atezolizumab-bevacizumab group).

Patient-Reported Outcomes

Time to deterioration in role functioning also favored atezolizumab plus bevacizumab over sorafenib (9.1 months vs 3.6 months). Clinically meaningful deterioration in physical functioning was reported by a smaller proportion of patients who received atezolizumab plus bevacizumab compared with sorafenib from day 1, cycle 2, until day 1, cycle 5.

The median time to deterioration in symptoms also significantly favored atezolizumab plus bevacizumab over sorafenib, including appetite loss, diarrhea, fatigue, jaundice, and pain.

“These patient-reported outcome data further support the positive benefit to risk profile of atezolizumab plus bevacizumab versus sorafenib and in a nice way complement the efficacy data in these patients with unresectable HCC for who have not received prior systemic therapy,” Dr Galle concluded.

The patient-reported outcomes with atezolizumab plus bevacizumab “bolster the case that IMbrave150 is practice-changing that we’ll likely be considering this [combination] for front-line therapy,” said invited discussant A. Craig Lockhart, MD, MHS, Chief, Division of Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center, FL.

Patient-reported outcomes add value to clinical trials, because they provide a comprehensive outcome measure in addition to overall survival, Dr Lockhart said. They can also assist with health-related economic value for expensive therapies, adding “economic impetus that this therapy, despite its expense, is having an impact on patients’ quality of life,” Dr Lockhart said.

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