Ruth He, MD, discusses major takeaways from the phase 3 IMbrave150 trial of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma.
Ruth He, MD:The approval of bevacizumab and atezolizumab has brought the first combination immunotherapy in the frontline treatment. IMbrave150 was a global phase 3 randomized study. Patients were randomized between the combination of bevacizumab and atezolizumab vs sorafenib in a 2:1 fashion with coprimary study end point PFS [progression-free survival] and OS [overall survival] by independent review. Almost all patients enrolled in IMbrave150 have Child-Pugh A liver function.
Most of the patients came out of Asia and has high-risk features. Notably, some of the patients have elevated alpha-fetoprotein, while over 70% of patients had vascular invasion or extrahepatic spread. The study was very well balanced in both arms. At the time of primary analysis, there was a median follow-up of 8.6 months that provided an improvement in OS with a hazard ratio of 0.58.
At the time of primary analysis, there was a median follow-up of 8.6 months that has shown that the combination of bevacizumab-atezolizumab provided the improvement in OS with a hazard ratio of 0.58 and a hazard ratio for PFS at 0.59. At the time of primary analysis, the median OS for the combination of bevacizumab-atezolizumab arm had not been reached. Moreover, updated data with a median follow-up of 15.6 months were presented at ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium]. The combination of bevacizumab-atezolizumab had a median OS of 19.2 months vs 13.4 months with sorafenib. The hazard ratio now is 0.66. The curves separated early and remained separated throughout the course of the study. Additionally, with a longer follow-up, and there being more responses with the combination than initially reported, the response rate now is 30%, including more complete responders now at 8%.
With a longer follow-up, there are more responses with the combination than initially reported. The response rate is 30%, which includes more complete responses, at 8%. This resulted in disease control of 74% with the combination vs 55% with sorafenib. The median duration of response with the combination is over 18 months. Moreover, with a longer follow-up, there are no new safety signals. There has been some increase in adverse events [AEs]. Specifically, there are grade 3/4 AEs, 63% with the combination vs 57% with sorafenib. Treatment-related grade 3/4 AEs include 43% with the combination vs 46% with sorafenib, probably reflecting the fact that patients have been on treatment longer.
The patient population enrolled in IMbrave150 had Child-Pugh A liver function and was required to have upper endoscopy prior to enrollment within 6 months. This regimen was very well tolerated. Numerically, the AEs were similar between the 2 arms. However, if you look at quality-of-life measures as well as patient-reported outcomes, the combination of bevacizumab and atezolizumab seems better tolerated per patient report.
Here are my personal experiences with the combination: I found that the safety and tolerability profile of the combination remained quite consistent with the known safety profile of each drug and the underlying disease. Before I start patients on the combination, I want to make sure they have no contraindication to bevacizumab or atezolizumab, in addition to making sure that the patients’ blood pressure is under control. I’ll make sure the patient gets an EGD [esophagogastroduodenoscopy] to evaluate and treat esophageal varices, in addition to a baseline urinalysis to screen for patients with underlying proteinuria from other etiologies, such as hypertension and diabetes. Finally, I will monitor immune-mediated toxicity and treat those toxicities accordingly.
Transcript edited for clarity.