Manageable Safety Across Treatment Periods for Durvalumab, Bevacizumab, and TACE Regimen Among Patients With Unresectable Hepatocellular Carcinoma

According to safety analyses from the phase 3 EMERALD-1, the combination of durvalumab, bevacizumab, and transarterial chemoembolization had a manageable safety profile across all treatment periods. These safety profiles were consistent with individual agents and underlying disease.

As previously reported, the primary end point of the global, phase 3 EMERALD-1 study was met, demonstrating an improvement of progression-free survival [PFS] with durvalumab, bevacizumab, and transarterial chemoembolization [TACE] when compared to placebos plus TACE, for patients with embolization-eligible unresectable hepatocellular carcinoma. Patients were randomized on a 1-to-1-to-1 basis to receive either durvalumab plus TACE, durvalumab plus bevacizumab plus TACE, or placebos plus TACE. This post hoc, exploratory analysis reports on safety in the 2 treatment periods of the study: durvalumab plus TACE, and durvalumab plus bevacizumab.

These data were first presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In the durvalumab-TACE period, patients received 1 to 4 of TACE (investigators choice: conventional TACE or DEB-TACE), plus 100 mg of durvalumab every 4 weeks, or placebo for durvalumab. The durvalumab-bevacizumab period followed the last TACE and patients received 1120 mg of durvalumab every 3 weeks plus 15 mg/kg of bevacizumab every 3 weeks, plus placebos if in placebo arm. Outcomes assessed were adverse events, start and end date, maximum or change in adverse event grade, and causality. These outcomes were evaluated in both treatment periods for any patient who received any study drug within the arm they were randomized.

The median exposure to durvalumab (or placebo) in all arms during the durvalumab-TACE period was 2.76 months. The median exposure to durvalumab during the durvalumab-bevacizumab period was 6.93 months in the durvalumab-TACE arm and 10.51 months in the durvalumab-bevacizumab-TACE arm. The median exposure to bevacizumab during the durvalumab-bevacizumab period was 9.35 in the durvalumab-bevacizumab-TACE arm.

In the durvalumab-TACE arm, 30.6% of patients experienced an adverse event possibly related to treatment during the durvalumab-TACE period, and 39.4% during the durvalumab-bevacizumab period. Adverse events were provoked by TACE in 37.3% of cases during the durvalumab-TACE period vs 8.3% in the durvalumab-bevacizumab period.

In the durvalumab-bevacizumab-TACE arm, 29.0% of patients experienced an adverse event possibly related to treatment during the durvalumab-TACE period, and 50.1% during the durvalumab-bevacizumab period. Adverse events were provoked by TACE in 46.6% of cases during the durvalumab-TACE period vs 9.3% in the durvalumab-bevacizumab period.

In the placebos-TACE arm, 20.5% of patients experienced an adverse event possibly related to treatment during the durvalumab-TACE period, and 34.5% during the durvalumab-bevacizumab period. Adverse events were provoked by TACE in 42.5% of cases during the durvalumab-TACE period vs 10.5% in the durvalumab-bevacizumab period.

Study authors concluded, “These data further support [durvalumab, bevacizumab,] and TACE as a new potential standard of care in embolization-eligible [unresectable hepatocellular carcinoma].”

Source:

Chan SL, Sangro B, Kudo M, et al. Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma. J Clin Oncol. 42(16):suppl.4122. doi:10.1200/JCO.2024.42.16_suppl.4122