Atezolizumab-bevacizumab combination delays quality-of-life deterioration in hepatocellular carcinoma
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Atezolizumab in combination with bevacizumab delayed time to deterioration of quality of life, physical functioning and role functioning compared with standard-of-care sorafenib as first-line treatment for unresectable hepatocellular carcinoma, according to patient-reported outcomes of the randomized phase 3 IMbrave 150 study scheduled for presentation at Gastrointestinal Cancers Symposium.
The combination also appeared to delay appetite loss, fatigue, pain and diarrhea.
“Because this combination demonstrated to be more efficacious than the previous standard of care and because it showed a favorable safety profile, it should become the new standard of care,” Peter Galle, MD, PhD, director of the medical department at University Medical Center Mainz in Germany and president-elect of the German Association for the Study of the Liver, told Healio.
Previous results of the IMbrave 150 study showed atezolizumab (Tecentriq, Genentech) plus bevacizumab (Avastin, Genentech) significantly improved PFS and OS compared with sorafenib (Nexavar, Bayer) among 501 patients with unresectable hepatocellular carcinoma who had not received previous systemic therapy.
Galle and colleagues reported data on patient-reported outcomes of the trial, in which researchers randomly assigned patients 2:1 to atezolizumab dosed at 1,200 mg IV plus bevacizumab dosed at 15 mg/kg once every 3 weeks or sorafenib dosed at 400 mg orally twice daily until loss of clinical benefit or unacceptable toxicity.
Patients completed two validated questionnaires for assessing quality of life, physical functioning and role functioning before treatment, every 3 weeks during treatment and every 3 months after treatment discontinuation or disease progression. Researchers defined time to deterioration (TTD), a prespecified secondary endpoint of the study, as a decrease of at least 10 points from baseline in patient-reported outcomes.
About 92% of patients in both cohorts completed the questionnaires from baseline through most of treatment.
Results showed that, compared with sorafenib, atezolizumab and bevacizumab delayed TTD in patient-reported quality of life (median, 11.2 months vs. 3.6 months; HR = 0.63; 95% CI, 0.46-0.85), physical functioning (median, 13.1 months vs. 4.9 months; HR = 0.53; 95% CI, 0.39-0.73) and role functioning (median, 9.1 months vs. 3.6 months; HR = 0.62; 95% CI, 0.46-0.84).
The combination also delayed TTD in patient-reported appetite loss, fatigue, pain and diarrhea compared with sorafenib. Additionally, a smaller proportion of patients in the combination group experienced clinically meaningful deterioration in each of these symptoms.
“Treatment after atezolizumab and bevacizumab [in patients who do not respond sufficiently] has not yet been investigated,” Galle said. “It is reasonable to use previous first-line treatments, such as sorafenib [Nexavar, Bayer] or lenvatinib [Lenvima, Eisai], but this is an opinion with only weak and indirect evidence.” – by John DeRosier
Reference:
Galle PR, et al. Abstract 476. Presented at: Gastrointestinal Cancers Symposium; Jan. 23-25, 2020; San Francisco.
Disclosures: F. Hoffman-La Roche Ltd. funded the study. Galle reports consultant/advisory roles with and/or travel expenses, honoraria or research funding from AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Eisai, Ipsen, Merck Sharp & Dohme and Sirtex Medical. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Vincent Chung, MD
Sorafenib, a VEGF inhibitor, has been the standard first-line treatment for patients with unresectable hepatocellular cancer for over a decade. Nivolumab (Opdivo, Bristol-Myers Squibb) was approved in the second-line setting after prior sorafenib use and has demonstrated impressive response rates, which have not been seen with sorafenib. Preclinical studies have demonstrated synergy with VEGF inhibitors and checkpoint inhibitors leading to numerous trials in various solid tumors. Results of the IMbrave 150 study, presented last year, showed bevacizumab plus atezolizumab improved survival over sorafenib as a single agent in the first-line setting.
Now, Galle and colleagues present patient-reported outcomes from this trial. In this era of value-based medicine, not only are we looking at survival benefit, but we also are looking at quality of life. For a treatment that may only improve survival by months, if quality of life is poor during that time, we are not doing our patients any favors. The study showed patients who received the combination therapy had a significant improvement in quality of life with good responses that I expect to continue. The combination is now under review by the FDA for approval as first-line therapy for patients with unresectable hepatocellular carcinoma. Based upon these impressive results, I expect this regimen will be approved.
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