1008P IMbrave150: Management of adverse events of special interest (AESIs) for atezolizumab (atezo) and bevacizumab (bev) in unresectable HCC

Abstract

Background: Conventional transarterial chemoembolization (cTACE) is an effective locoregional therapy in hepatocellular carcinoma (HCC). We evaluated variations around cTACE in a-fetoprotein (AFP), circulating cell-free and tumor DNA (cfDNA and ctDNA) as a marker of therapeutic response.Methods: This prospective monocentric study enrolled consecutive patients treated by cTACE with samples collected at baseline (D-1), day 2 (D+2) and at 1 month (M+1). All cTACE were carried out by only one interventional radiologist and according to the same procedure using farmorubicin drug. cfDNA was quantified by fluorometric method and ctDNA by digital Polymerase Chain Reaction designed for two-hotspot TERT mutations. CT-scan or MRI were performed at M+1 following cTACE and independently reviewed. The objective was to identified by ROC curves the thresholds of cfDNA, ctDNA and AFP variations associated with progression.Results: A total of 38 patients was included from March 2018 to March 2019. All except one had cirrhosis and alcohol was the most frequent etiology of HCC (73.7%). A total of 24/38 (63.2%) patients were naïve for TACE. At M+1, 33/38 patients (86.8%) had a controlled disease and 5/38 (13.2%) a progressive disease (PD). ctDNA was detectable in 16/38 (42.1%) patients at D-1, 30/38 (78.9%) at D+2 and 14/35 (40.0%) at M+1 and cfDNA median value was 21.6 ng/mL, 82.3 ng/mL and 17.8 ng/mL, respectively. All markers significantly increased from D-1 to D+2 (p<0.005) and cfDNA and ctDNA significantly decreased from D+2 to M+1, (p<0.0001). The analysis of variations from D-1 to M+1 identified that thresholds at +31.4% for cfDNA and 0% for ctDNA were significantly associated with PD at M+1, 44.4% (>+31.4%) vs. 3.8% (<¼+31.4%) and 50.0% (>0%) vs. 5.0% (<¼0%), respectively. No significant threshold was identified for AFP. Using a score combining both cfDNA and ctDNA (n¼28), patients were classified into high (n¼5) or low-risk (n¼23) of PD at M+1 with a PD rate of 80.0 % vs 4.3% (p¼0.001) and a median progression-free survival of 1.3 vs 10.3 months (p¼0.002), respectively.Conclusions: This study suggests that cfDNA and ctDNA increases around TACE procedure are associated with therapeutic failure.Legal entity responsible for the study: The authors.

Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

“…An analysis of time to onset of first AEs of particular relevance with atezolizumab and bevacizumab in the IMbrave150 study showed that the earliest atezolizumab-defined AEs were infusion-related reaction (onset at median 0.7 months), pancreatitis (1.4 months), and hepatitis (1.6 months); rash and hyperthyroidism occurred at a median of 2.7 months, hypothyroidism at 3.5 months, and diabetes mellitus at 4.4 months. 39 The earliest bevacizumab-defined AE was hypertension (onset at median 1.5 months), followed by proteinuria and venous thromboembolic events at 2.8 months, bleeding or haemorrhage at 3.3 months, and arterial thromboembolic events at 4.7 months. 39 The onset of GI symptoms is most commonly 5–10 weeks after initiation of immune checkpoint inhibition.…”

“…39 The earliest bevacizumab-defined AE was hypertension (onset at median 1.5 months), followed by proteinuria and venous thromboembolic events at 2.8 months, bleeding or haemorrhage at 3.3 months, and arterial thromboembolic events at 4.7 months. 39 The onset of GI symptoms is most commonly 5–10 weeks after initiation of immune checkpoint inhibition. 57…”

“…AEs of particular relevance to bevacizumab (the known adverse drug reactions of hypertension, bleeding or haemorrhage, proteinuria, and venous or arterial thromboembolic events) occurred in 57.8% of patients receiving atezolizumab plus bevacizumab and 48.7% of patients receiving sorafenib. 39…”

Immunotherapy of advanced hepatocellular carcinoma: case report and literature review

“…2022;16 (9): [31][32][33][34][35][36][37][38][39] At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs.…”

“…В исследовании IMbrave150 кровотечения как осложнения лечения зарегистрированы у 25% больных на комбинированной терапии «атезолизумаб + бевацизумаб» и в 17% случаев в группе сорафениба, однако геморрагические осложнения 3-4-й степени регистрировались одинаково -в 6% в обеих группах 1 [24,[34][35][36][37].…”