Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial
Mené dans 17 pays sur 501 patients atteints d'un carcinome hépatocellulaire non résécable, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité du sorafénib et d'un traitement combinant atézolizumab et bévacizumab
Background : Understanding patients' experience of cancer treatment is important. We aimed to evaluatepatient-reported outcomes (PROs) with atezolizumab plus bevacizumab versus sorafenibin patients with advanced hepatocellular carcinoma in the IMbrave150 trial, whichhas already shown significant overall survival and progression-free survival benefitswith this combination therapy. Methods : We did an open-label, randomised, phase 3 trial in 111 hospitals and cancer centres across 17 countries or regions. We included patients aged 18 years or older with systemic,treatment-naive, histologically, cytologically, or clinically confirmed unresectablehepatocellular carcinoma and an Eastern Cooperative Oncology Group (ECOG) performancestatus of 0 or 1, with disease that was not amenable to curative surgical or locoregionaltherapies, or progressive disease after surgical or locoregional therapies. Participantswere randomly assigned (2:1; using permuted block randomisation [blocks of six], stratifiedby geographical region; macrovascular invasion, extrahepatic spread, or both; baselinealpha-fetoprotein concentration; and ECOG performance status) to receive 1200 mg atezolizumabplus 15 mg/kg bevacizumab intravenously once every 3 weeks or 400 mg sorafenib orallytwice a day, until loss of clinical benefit or unacceptable toxicity. The independentreview facility for tumour assessment was masked to the treatment allocation. Previouslyreported coprimary endpoints were overall survival and independently assessed progression-freesurvival per Response Evaluation Criteria in Solid Tumors 1.1. Prespecified secondaryand exploratory analyses descriptively evaluated treatment effects on patient-reportedquality of life, functioning, and disease symptoms per the European Organisation forResearch and Treatment of Cancer (EORTC) quality-of-life questionnaire for cancer(QLQ-C30) and quality-of-life questionnaire for hepatocellular carcinoma (QLQ-HCC18).Time to confirmed deterioration of PROs was analysed in the intention-to-treat population;all other analyses were done in the PRO-evaluable population (patients who had a baselinePRO assessment and at least one assessment after baseline). The trial is ongoing;enrolment is closed. This trial is registered with ClinicalTrials.gov, NCT03434379. Findings : Between March 15, 2018, and Jan 30, 2019, 725 patients were screened and 501 patientswere enrolled and randomly assigned to atezolizumab plus bevacizumab (n=336) or sorafenib(n=165). 309 patients in the atezolizumab plus bevacizumab group and 145 patientsin the sorafenib group were included in the PRO-evaluable population. At data cutoff(Aug 29, 2019) the median follow-up was 8·6 months (IQR 6·2–10·8). EORTC QLQ-C30 completionrates were 90% or greater for 23 of 24 treatment cycles in both groups (range 88–100%in the atezolizumab plus bevacizumab group and 80–100% in the sorafenib group). EORTCQLQ-HCC18 completion rates were 90% or greater for 20 of 24 cycles in the atezolizumabplus bevacizumab group (range 88–100%) and 21 of 24 cycles in the sorafenib group(range 89–100%). Compared with sorafenib, atezolizumab plus bevacizumab reduced therisk of deterioration on all EORTC QLQ-C30 generic cancer symptom scales that wereprespecified for analysis (appetite loss [hazard ratio (HR) 0·57, 95% CI 0·40–0·81],diarrhoea [0·23, 0·16–0·34], fatigue [0·61, 0·46–0·81], pain [0·46, 0·34–0·62]), andtwo of three EORTC QLQ-HCC18 disease-specific symptom scales that were prespecifiedfor analysis (fatigue [0·60, 0·45–0·80] and pain [0·65, 0·46–0·92], but not jaundice[0·76, 0·55–1·07]). At day 1 of treatment cycle five (after which attrition in thesorafenib group was more than 50%), the mean EORTC QLQ-C30 score changes from baselinein the atezolizumab plus bevacizumab versus sorafenib groups were: –3·29 (SD 17·56)versus –5·83 (20·63) for quality of life, –4·02 (19·42) versus –9·76 (21·33) for rolefunctioning, and –3·77 (12·82) versus –7·60 (15·54) for physical functioning. Interpretation : Prespecified analyses of PRO data showed clinically meaningful benefits in terms ofpatient-reported quality of life, functioning, and disease symptoms with atezolizumabplus bevacizumab compared with sorafenib, strengthening the combination therapy'spositive benefit–risk profile versus that of sorafenib in patients with unresectablehepatocellular carcinoma.
The Lancet Oncology 2021