Therapy with atezolizumab (atezo) plus bevacizumab (bev) in systemic treatment (tx)-naive patients (pts) with unresectable HCC in IMbrave150 resulted in significantly longer survival compared with sorafenib (sor) (NCT03434379; Finn NEJM 2020). A further 12 months of follow-up confirmed the durability of this clinically significant tx effect (Finn ASCO GI 2021). Patients who continued to receive atezo after radiological progression and until clinical benefit was no longer achieved are reported on for efficacy and safety. Patients received either atezo 1,200 mg IV plus bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or lack of clinical benefit as determined by the investigating physician (INV).

Patients with progressing disease (PD) under INV RECIST 1.1 (not at a key anatomical site) could continue trial tx if there was a therapeutic benefit. Patients with PD who were initially treated with atezo and continued on atezo were considered. Researchers found that 236 out of 336 patients who received atezo plus bev had PD; of these, 130 kept taking atezo (without bev), 60 switched to another treatment, and 46 didn’t receive any treatment at all on or after their first episode of PD. Patients who persisted on atezo were more likely to be in Child-Pugh A5 (78%) and Barcelona Clinic Liver Cancer (BCLC) stage C (80%) categories than those who received alternative treatment (85% BCLC stage C, 72% Child-Pugh A5). Post-PD, the most prevalent alternative txs for patients who continued atezo and those who received other tx were sor (13%) and lenvatinib (35%). In the group of patients who got at least 10 cycles of atezo after PD, the median number of cycles was 5, with a range of 1 to 33. Among the ITT group, 180 of 336 patients (54%) who received atezo plus bev compared to 60 of 130 (46%) who continued on atezo alone.

Baseline (BL) and progression (PD) data on efficacy are tabulated below. 30 (23%) patients who persisted on atezo experienced grade 3/4 adverse events (AEs), while 21 (16%) patients experienced grade 3/4 AEs attributable to the treatment. All 6 of the Grade 5 adverse events (AEs) that occurred were unrelated to the treatment. Patients with unresectable HCC are typically treated with atezo with bev. Patients in IMbrave150 who continued to benefit clinically from atezo after PD may have reaped additional benefits from continuing treatment, but interpretation is constrained by selection bias (prespecified criteria excluding pts with loss of clinical benefit). Based on these findings, it appears that continuing atezo treatment past the point of diminishing therapeutic effect may improve post-PD outcomes. Besides this pilot study in a subset of patients, IMbrave251 will prospectively evaluate the benefit of tx with atezo in the face of formal progression (NCT04770896).

Source – ASCO GI 2023