975P - The clinical impact of urinary protein creatinine ratio and AFP at six weeks in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Background

In systemic therapy for unresectable HCC (u-HCC), atezolizumab plus bevacizumab (Atez+Bev) has become a standard first-line therapy. Although previous studies already reported predictive biomarkers, including neutrophil-lymphocyte ratio (NLR), CRP, and IL-6, there are no established markers in real-world practice. Urinary protein creatinine ratio (UPCR) was reported to be associated with IL-6. We investigated universal predictive markers in the early phase after the administration of Atez+Bev.

Methods

A total of 134 patients who received Atez+Bev at our institution between Oct 2020 and Mar 2023 were enrolled. Tumor assessments by RECIST v1.1 were done using dynamic CT or MRI every 6-12 weeks. Blood and urine examinations, including UPCR and AFP, were performed every 3 weeks. All clinical information was analyzed retrospectively.

Results

The median age of the patients was 74 years, and the median ALBI score was -2.24. The line of treatment was 1^st (n=84) and 2^nd or later line (n=50). Seventy-eight (58%) patients were BCLC stage B, and 56 were stage C. The median follow-up duration was 11.2 months. The median overall survival (OS) was 24.5 months in 1^st line and 21.8 months in 2^nd or later line. The median progression-free survival (PFS) was significantly longer in 1^st line than in 2^nd or later line (8.2 vs. 4.2 months, p=0.01). The independent factors significantly associated with OS were pretreatment ALBI score (HR 4.8, 95%CI 2.2-10.4, p<.0001) and AFP ≥ 400ng/mL (HR 2.6, 95%CI 1.4-5.0, p=0.003). The independent factors associated with PFS in 1^st line were AFP decrease at 6 weeks (HR 0.41, 95%CI 0.2-0.9, p=0.03) and UPCR at 6 weeks (HR 1.3, 95%CI 1.3-2.8, p=0.002). Among the 1st-line patients with stable disease at 6-12 weeks (n=36), the patients with low UPCR (<0.24) at 6 weeks (N=27) had significantly longer PFS than those with high UPCR (11.3 vs. 4.6 months, p=0.02). The dose of Bev within 12 weeks was not significantly different between the two groups.

Conclusions

The assessments of early changes in UPCR and AFP during Atez+Bev were valuable. The therapeutic strategies for patients with stable disease at 6-12 weeks would be considered based on the changes in UPCR and AFP at 6 weeks.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Masayuki Kurosaki.

Funding

Has not received any funding.

Disclosure

K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, Eli Lilly. M. Kurosaki: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, Eli Lilly, Bayer, AstraZeneca. N. Izumi: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, Eli Lilly, Bayer, AstraZeneca. All other authors have declared no conflicts of interest.