Patient-Reported Outcomes With Atezolizumab/Bevacizumab Indicative of Benefit in Unresectable HCC

Atezolizumab (Tecentriq) plus bevacizumab (Avastin) was found to increase quality of life and improve disease symptoms in patients with unresectable hepatocellular carcinoma (HCC) over sorafenib (Nexavar), according to patient-reported outcomes (PROs) data from the phase 3 IMbrave150 trial (NCT03434379).

The European Organization Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer (QLQ-C30) survey identified that atezolizumab plus bevacizumab was associated with reduced risk of deterioration compared with sorafenib on all prespecified scales (HR, 0.57; 95% CI 0.40-0.81). This included diarrhea (HR, 0.23; 95% CI, 0.16-0.34), fatigue (HR, 0.61; 95% CI, 0.46-0.81), and pain (HR, 0.46; 95% CI, 0.34-0.62). In the quality-of-life questionnaire for HCC (QLQ-HCC18) survey, there were 2 disease specified symptoms for analysis, including fatigue (HR, 0.60; 95% CI, 0.45-0.80) and pain (HR, 0.65; 95% CI, 0.46-0.92), although jaundice was not included (HR, 0.76; 95% CI, 0.55-1.07).

On day 1 of cycle 5, the mean score changes from baseline for quality of life were -3.29 (SD, 17.56) for the atezolizumab plus bevacizumab cohort vs -5.83 (SD, 20.63) in the sorafenib cohort. Additionally, the changes for role functioning were -4.02 (SD, 19.42) compared with -9.76 (SD, 21.33) in each group, respectively, and -3.77 (SD, 12.82) vs -7.60 (SD, 15.54) for physical functioning, respectively.

“Regarding our first objective, based on high questionnaire completion rates, atezolizumab plus bevacizumab provided consistent and clinically meaningful benefits compared with sorafenib in several prespecified and post-hoc analyses of patient- reported quality of life, functioning, and disease symptoms,” wrote investigators of the study.

The IMbrave150 trial, which set out to assess the overall survival (OS) and progression-free survival (PFS) of the combination vs sorafenib, also aimed to determine the patient experience for those with HCC who were treated with atezolizumab/bevacizumab. As such, PROs were evaluated as part of a prespecified secondary and exploratory end points.

The open-label trial was conducted in 111 hospitals in 17 different countries. In order to enroll, participants needed to have an ECOG performance status of 0 or 1 as well as a Child-Pugh A score, and adequate hematologic and organ function.

In total, 501 patients were enrolled to receive either atezolizumab plus bevacizumab (n=336) group or sorafenib (n=165) group. Patients received 1200 mg of atezolizumab plus 15 mg/kg bevacizumab intravenously once every 3 weeks, or 400 mg of oral sorafenib twice a day. Treatment continued until loss of clinical benefit or unacceptable toxicity. However, researchers allowed patients to continue treatment beyond disease progression if there was a clinical benefit. Patients were required to have a CT or MRI scan every 6 weeks until week 54 and every 9 weeks after to assess tumors.

There were two questionnaires handed out to patients before the first day of each cycle, including the EORTC QLQ-C30 and the QLQ-HCC18. Patients needed to complete the questionnaire before meeting with physicians to discuss their health or laboratory results.

The coprimary end points of the trial were OS and PFS. Secondary endpoints included objective response rate and duration of response and secondary PRO end points consisted of deterioration of quality of life, physical functioning, and role functioning.

Both treatment groups reported better health status at baseline and better patient-reported health status during treatment. These were associated with a lower risk of progression or death. This study is still currently ongoing. 

Reference

Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial Lancet Oncol. Published online ahead of print, May 27, 2021;S1470-2045(21):00151-0. doi:10.1016/S1470-2045(21)00151-0