QoL Superior With Atezolizumab/Bevacizumab Versus Sorafenib in Frontline HCC

January 28, 2020
Wayne Kuznar

Analysis of patient-reported outcomes from the phase III IMbrave 150 study showed meaningful benefits in quality of life, functioning, and key symptoms with atezolizumab plus bevacizumab compared with sorafenib as first-line treatment in patients with unresectable hepatocellular carcinoma.

Peter Galle, PhD

Analysis of patient-reported outcomes from the phase III IMbrave 150 study showed meaningful benefits in quality of life (QoL), functioning, and key symptoms with atezolizumab (Tecentriq) plus bevacizumab (Avastin) compared with sorafenib (Nexavar) as first-line treatment in patients with unresectable hepatocellular carcinoma (HCC).

Compared with sorafenib, atezolizumab plus bevacizumab extended the median time to several symptoms, including appetite loss, fatigue, pain, jaundice, and diarrhea, said Peter Galle, PhD, at the 2020 Gastrointestinal Cancers Symposium.1

Patient-reported outcomes were prespecified endpoints included in the IMbrave 150 study design, noted Galle, director of gastroenterology, University Medical Center Mainz, Germany.

“Quality of life matters,” he said. “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 lifespan…the quality of life in the remaining lifespan 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.”

Baseline QoL scores were well-balanced between the 2 treatment arms (71.04 in the atezolizumab/bevacizumab arm and 68.79 in the sorafenib arm), “and patients started at a relatively high level, so in essence they were in relatively good shape,” he said. High and similar baseline scores were also reported in the physical functioning and role functioning domains in both arms.

Time to deterioration of QoL was extended from a median of 3.6 months in the sorafenib arm to 11.2 months in the atezolizumab plus bevacizumab arm (HR, 0.63; 95% CI, 0.46-0.85). This difference “was quite remarkable,” said Galle. Time to deterioration was defined as the time from randomization to first decrease from baseline ≥10 points in the global health status/QoL scale of the ERTC QLQ-C30 maintained for 2 consecutive assessments or 1 assessment followed by death from any cause within 3 weeks. Baseline QoL scores were similar between the 2 groups.

A change in QoL from baseline ≥10 points has been perceived by patients to be clinically meaningful. Using this threshold, 44.2% of the sorafenib arm had clinically meaningful deterioration in QoL on day 1 of cycle 2, compared with only 29.9% of the atezolizumab plus bevacizumab arm. By day 1, cycle 5, 35.7% of the sorafenib group and 29.6% of the atezolizumab plus bevacizumab group had clinically meaningful deterioration in QOL.

The median time to deterioration of physical functioning was also superior with atezolizumab plus bevacizumab: 13.1 months in the atezolizumab/bevacizumab arm versus 4.9 months in the sorafenib arm (HR, 0.53; 95% CI, 0.39-0.73). Clinically meaningful (≥10 points) deterioration in physical functioning occurred in 39.5% of sorafenib recipients at day 1, cycle 2 versus only 24.2% of the atezolizumab/bevacizumab arm. This advantage to atezolizumab plus bevacizumab was sustained through day 1, cycle 5, at which time 31.4% of the sorafenib group and 22.9% of the atezolizumab/bevacizumab experienced clinically significant deterioration.

Time to deterioration in role functioning also favored atezolizumab/bevacizumab over sorafenib (9.1 vs 3.6 months; HR, 0.62; 95% CI, 0.46-0.84). Clinically meaningful deterioration in physical functioning was reported by 41.1% of the sorafenib group at day 1, cycle 2 compared with 29.3% of the atezolizumab plus bevacizumab group. This advantage to atezolizumab plus bevacizumab diminished over time but was still present at day 1, cycle 5, at which time 31.4% of the sorafenib arm and 28.1% of the atezolizumab/bevacizumab arm reported clinically meaningful deterioration.

Time to deterioration in symptoms also favored atezolizumab plus bevacizumab:

  • The median time to appetite loss was not estimable in the atezolizumab/bevacizumab arm versus 7.62 months in the sorafenib arm (HR, 0.57; 95% CI, 0.40-0.81)
  • Median time to diarrhea was not estimable in the atezolizumab/bevacizumab arm compared with 4.44 months in the sorafenib arm (HR, 0.23; 95% CI, 0.16-0.34)
  • Median time to fatigue, as measured by the QLQ-C30, was 5.68 months with atezolizumab/bevacizumab compared with 2.10 months with sorafenib (HR, 0.61; 95% CI, 0.46-0.81)
  • On the QLQ-HCC18 scale, median time to fatigue was 5.65 months versus 2.14 months in the atezolizumab/bevacizumab and sorafenib arms, respectively (HR, 0.60; 95% CI, 0.45-0.80)
  • Median time to jaundice in the 2 treatment arms was 10.55 months versus 6.47 months, respectively (HR, 0.76; 95% CI, 0.55-1.07)
  • Median time to pain on the QLQ-C30 scale was 9.72 months versus 2.79 months, respectively (HR, 0.46; 95% CI, 0.34-0.62)
  • On the QLQ-HCC18 scale, median time to pain was not estimable in the atezolizumab/bevacizumab arm compared with 9.82 months in the sorafenib arm (HR, 0.65; 95% CI, 0.46-0.92).

In IMbrave 150, 501 patients were randomized 2:1 in an open-label fashion to atezolizumab at 1200 mg IV every 3 weeks plus bevacizumab at 15 mg/kg IV every 3 weeks, or sorafenib at 400 mg orally twice daily, until loss of clinical benefit or unacceptable toxicity. Patients completed the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires before at baseline, every 3 weeks on treatment, and every 3 months after treatment discontinuation or disease progression.

Questionnaire completion rates were ≥92% in both arms from baseline through most of the treatment period.

The coprimary endpoints of IMbrave 150, reported previously, were overall survival and progression-free survival, both of which were improved significantly with atezolizumab/bevacizumab versus sorafenib. There was a 42% (HR, 0.58; 95% CI, 0.42-0.79; P = .0006) decreased risk of death and a 41% (HR, 0.59; 95% CI, 0.47-0.76; P <.0001) decreased risk of disease progression or death in the atezolizumab/bevacizumab arm versus the sorafenib arm.2

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

References

  1. Galle P, Finn RS, Qin S, et al. Patient-reported outcomes (PROs) from the Phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). Presented at GI Cancers Symposium; January 23-25, 2020; San Francisco, CA. Abstract 476.
  2. Cheng A-L, Qin S, Ikeda M, et al. IMbrave150: Efficacy and Safety Results From a Ph 3 Study Evaluating Atezolizumab (atezo) + Bevacizumab (bev) vs Sorafenib (Sor) as First Treatment (tx) for Patients (pts) With Unresectable Hepatocellular Carcinoma (HCC). Presented at ESMO Asia 2019 Congress; November 22-24, 2019; Singapore. Abstract LBA3.

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