Stopping the effects of VEGF and PD-L1 caused by TACE is a good thing, it turns out.
Adding durvalumab plus bevacizumab to TACE led to significant improvements in progression-free survival among hepatocellular carcinoma patients compared to those who underwent TACE alone.
Hepatocellular carcinoma patients who are not eligible for therapies with curative intent are typically treated with transarterial chemoembolisation in an attempt to reduce tumour burden and delay disease progression. But as the procedure increases vascular endothelial growth factor and tumour PD-L1 expression – meaning residual tumour tissue can survive – progression-free survival in patients treated with TACE is poor.
The EMERALD-1 trial sought to test the rationale of using anti-VEGF and anti-PD-L1 systemic therapies in combination with TACE at an earlier point in treatment. The findings, published in The Lancet, found that combining durvalumab and bevacizumab with TACE improved the median progression-free survival by seven months compared to TACE and placebo.
“The consistent improvements with durvalumab plus bevacizumab versus placebo alone across progression-free survival, time to progression and objective response rate are clinically relevant in this setting, where treatment goals include controlling tumour growth, reducing tumour burden, and delaying progression,” the authors wrote.
Over 600 patients with hepatocellular carcinoma were recruited from more than 150 medical centres across 18 countries and randomised to receive TACE in combination with both durvalumab and bevacizumab, durvalumab and placebo or placebo alone. There was no limit to the number of TACE procedures a patient could undergo.
Patients who received durvalumab and bevacizumab in addition to TACE had better progression-free survival compared to patients who received TACE and placebo (median 15 versus eight months). Receiving durvalumab and placebo did not improve progression-free survival relative to placebo (median 10 months versus 8 months).
“The combination of durvalumab immunotherapy plus bevacizumab anti-VEGF therapy appears to be important for maximising efficacy,” the authors noted.
“Non-significant numerical improvements in progression-free survival, time to progression (not formally tested for significance) and objective response rate (not formally tested for significance) were observed with durvalumab plus placebo versus placebo; as such, further investigation into subgroups that might benefit from durvalumab plus TACE is warranted.”
Related
Adverse events were reported by more than 90% of patients in each treatment group, with a larger proportion of patients in the durvalumab-bevacizumab group experiencing treatment-related adverse events (81%) compared to patients who received durvalumab and placebo (50%) or placebo alone (45%). The most commonly reported adverse events were post-embolisation syndrome, hypothyroidism, pruritus, hypertension, constipation and proteinuria.
The authors were not concerned by the adverse event figures.
“In combination with TACE, the safety profile of durvalumab and bevacizumab was manageable and consistent with the known safety profiles of durvalumab, bevacizumab, and TACE in unresectable hepatocellular carcinoma and the underlying liver disease,” they said.
“Among 154 participants who received durvalumab and bevacizumab, 16 (10%) had an adverse event with the outcome of death; however, none of these events were considered by the investigator to be related to study treatment, and might therefore be linked to the competing risk of death from, for example, cirrhosis, cancer or other factors.”
