HCC: Atezolizumab Plus Bevacizumab Significantly Improved Outcomes

Patients with treatment-naïve unresectable hepatocellular carcinoma reported that treatment with atezolizumab plus bevacizumab brought about significant, clinically meaningful benefits in quality of life, physical functioning, and disease symptoms—more so than treatment with sorafenib, according to an analysis of patient-reported outcomes from the IMbrave150 trial published in The Lancet Oncology.

“Patient-reported outcomes (PROs) are increasingly recognized as an essential endpoint in cancer clinical trials because they provide information about the full, direct effect of treatment on the patient experience. PROs have also been linked with overall survival in numerous cancer studies and can provide prognostic information beyond standard clinical measures. In patients with hepatocellular carcinoma, cancer-related and treatment-related symptoms and their associated effect on day-to-day functioning and health-related quality of life are complex,” wrote Peter R. Galle, MD, of the University Medical Center, Mainze, Germany, and colleagues.

“Despite advances in systemic hepatocellular carcinoma treatment and the increasing availability of information about treatment side-effects, little is known about the direct effect of hepatocellular carcinoma treatments on the patient experience, and few full reports of prospective analyses of PROs with recently developed systemic hepatocellular carcinoma treatments have been published to date,” they added.

The IMbrave150 trial was an open-label, randomized, phase III trial conducted in 111 hospitals and cancer centers throughout 17 countries/regions—the analysis included patients with systemic, treatment-naïve unresectable hepatocellular carcinoma with an Eastern Cooperative Oncology Group (ECOG) performance states of 0 or 1 who were not candidates for curative surgical or locoregional treatment, or those with progressive disease after such treatment. Patients were randomized to treatment with atezolizumab plus bevacizumab ((1,200 mg and 15 mg/kg, respectively, every 3 weeks) or treatment with sorafenib (400 mg orally twice daily).

Original results from the IMbrave150 study demonstrated significant benefits in overall and progression-free survival in patients treated with atezolizumab plus bevacizumab compared with sorafenib, the standard of care. Researchers concluded that, based on these findings, the combination treatment should be considered the standard of care in this setting.

For this evaluation of patient-reported outcomes, Galle and colleagues included 454 patients followed for a median of 8.6 months. They assessed prespecified secondary and exploratory analyses of effects on patient-reported quality of life, functioning, and disease symptoms per the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire for cancer (QLQ-C30) and quality-of-life questionnaire for hepatocellular carcinoma (QLQ-HCC18).

Atezolizumab plus bevacizumab reduced the risk of deterioration on all EORTC QLQ-C30 generic cancer symptom scales, including:

• Loss of appetite (H: 0.57; 95% CI: 0.40-0.81).
• Diarrhea (HR: 0.23; 95% CI: 0.16-0.34).
• Fatigue (HR: 0.61; 95% CI: 0.46-0.81).
• Pain (HR: 0.46; 95% CI: 0.34-0.620).
• Two of three disease-specific symptom scales from the EORTC QLQ-HCC18 questionnaire: fatigue (0.60; 95% CI: 0.45-0.80) and pain (HR: 0.65; 95% CI: 0.46-0.92), but not jaundice (HR: 0.76; 95% CI: 0.55-1.07).

By day one of treatment cycle 5, mean EORTC QLQ-30 score changes from baseline in patients treated with atezolizumab plus bevacizumab compared with those treated with sorafenib were significantly improved, as follows:

• Quality of life: −3.29 versus −5.83, respectively.
• Role functioning: −4.02 versus −9.76.
• Physical functioning: −3.77 versus −7.60.

Galle and colleagues noted that patients with hepatocellular carcinoma also frequently have chronic liver disease, which increases the likelihood that they will experience drug related toxicities and overall deterioration. Therefore, understanding the effects of new systemic treatments can help clinicians better individualize optimal treatments and management strategies in these patients.

“These data strengthen the positive benefit–risk profile of first-line atezolizumab plus bevacizumab versus that of sorafenib in patients with unresectable hepatocellular carcinoma, and should underpin the adoption of atezolizumab plus bevacizumab as the standard of care in this indication,” they concluded.

In their accompanying editorial, Nicola Personeni, MD, and Lorenzo Rimassa, MD, both of the Humanitas University and Humanitas Cancer Center, IRCCS Humanitas Research Hospital, in Milan, Italy, commended these researchers for their work and called for more studies on patient-reported outcomes.

“The work of Galle and colleagues provides valuable guidance by introducing a baseline analysis of patient-reported outcomes that identifies patients who are likely to derive benefit from systemic treatment, regardless of the individual type of treatment. However, several hurdles need to be addressed before patient-reported outcomes can be used in daily practice. With additional health-related quality-of-life analyses that will further convey patients’ voices into prospective investigation level, a deeper insight is expected to better inform our strategies across the therapeutic landscape for hepatocellular carcinoma,” they wrote.

Study limitations include its open-label design and the descriptive rather than qualitative nature of patient-reported endpoints. Galle and colleagues also noted that there was “no assessment of treatment-related symptoms from the patient perspective, precluding appropriate exploration of how the toxicity profiles of the two regimens might have influenced the observed PRO results.”

1. Treatment with atezolizumab plus bevacizumab brought about consistent and clinically meaningful benefits compared with sorafenib in several prespecified and post-hoc analyses of patient-reported quality of life, function, and symptoms in patients with treatment-naïve unresectable hepatocellular carconima.

2. Patient-reported outcomes are important to consider in the search for optimal patient treatment and management strategies.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

Cat ID: 120

Topic ID: 78,120,730,111,120,192,925