Peter R. Galle, MD, PhD, discusses the PROs analysis from the IMbrave150 trial in HCC and the importance of understanding patient experience during treatment.
Peter R. Galle, MD, PhD
An analysis of the phase III IMbrave150 trial in hepatocellular carcinoma (HCC) demonstrated the clinical importance of measuring patient-reported outcomes (PROs) to gain insight on the impact of treatment on patients' quality of life (QOL), said Peter R. Galle, MD, PhD.
"PROs are relevant," said Galle. "In the past, PROs have been slightly neglected, particularly in patients with HCC. We have seen many failures; there were many phase III trials that did not result in positive outcomes. Some of the therapeutic options were just too toxic. This shows us the importance of paying attention to the impact [of treatment] on the tumor and the patient."
The PRO analysis showed a clinically meaningful benefit in time to deterioration in QOL, role and physical functioning, and symptoms with the first-line combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) compared with sorafenib (Nexavar) in patients with unresectable HCC.1 The combination elicited a prolonged median time to deterioration in several key symptoms, including loss of appetite, fatigue, pain, jaundice, and diarrhea. Moreover, the median time to deterioration in QOL was 11.2 months with atezolizumab/bevacizumab versus 3.6 months with sorafenib (HR, 0.63; 95% CI, 0.46-0.85).
On day 1 of cycle 2 of therapy, 29.9% of patients treated with atezolizumab/bevacizumab experienced a clinically meaningful deterioration in QOL from baseline, defined as ≥10 points. At the same time point, 44.2% of patients experienced a clinically meaningful deterioration in QOL with sorafenib. By day 1 of cycle 5, 29.6% and 35.7% of patients experienced a deterioration on atezolizumab/bevacizumab and sorafenib, respectively.
The median time to deterioration of physical functioning and median time to deterioration of role functioning both favored atezolizumab/bevacizumab versus sorafenib.
In January 2020, a supplemental biologics license application was submitted to the FDA for the combination of atezolizumab and bevacizumab for the treatment of patients with unresectable HCC who have not received prior systemic therapy. The application is based on findings from the IMbrave150 study, in which the combination led to a 42% reduction in the risk of death compared with sorafenib.2
In an interview with OncLive, Galle, director of the Medical Department at the University Medical Center Mainz and president-elect of the German Association for the Study of the Liver, discussed the PROs analysis from the IMbrave150 trial in HCC and the importance of understanding patient experience during treatment.
OncLive: Could you shed light on the data that have been reported from the IMbrave150 trial?
Galle: The IMbrave150 trial was a first-line study assessing the combination of atezolizumab and bevacizumab versus sorafenib in patients with unresectable HCC.
Efficacy data presented at the 2019 ESMO Asia Congress demonstrated superiority in overall survival (OS) and progression-free survival (PFS) with the combination of atezolizumab plus bevacizumab.
At the 2020 Gastrointestinal Cancers Symposium, we reported the PROs, QOL, role functioning, physical function, and symptoms [for patients in the IMbrave150 trial].
What were some of the key endpoints that were assessed in the trial?
The co-primary endpoints of the study were OS and PFS. A key secondary endpoint was objective response rate. [All endpoints were] in favor of the combination.
An additional secondary endpoint was time-to-deterioration in PROs. That was measured by the EORTC QLQ-C30 questionnaire. A drop of ≥10 points was considered to be clinically meaningful.
In all of these aspects—QOL, physical functioning, and role functioning—there was a delay and lower rate of deterioration in favor of atezolizumab/bevacizumab.
What were the results of the PROs analysis?
We learned that at each cycle of therapy where [PROs were assessed] compared with baseline, a lower proportion of patients in the combination arm showed a deterioration compared with sorafenib. [Simply put], the combination was better tolerated and patients in the combination arm had better QOL.
Did other measurement scales show similar findings?
The data were consistent with different [assessment scales]. Also, there was a questionnaire-specific exploratory analysis that assessed patient symptoms. These symptoms, which included fatigue, jaundice, pain, and others, were also delayed [with the combination] compared with sorafenib.
What are the implications of this research?
The implication is that we now have not only an effective treatment for patients with HCC, but we have a well-tolerated therapy. This is a nice addition to [the armamentarium] and provides an effective option for patients without [increased toxicity].
It is increasingly accepted that PROs are relevant. Whatever treatment you select, you need to hear the patient's voice in order to learn whether the impact on the tumor is coming at too high a cost to the patient.