Organ-specific responses to atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma.

Abstract

4076 Background: Anti-PD-1 monotherapy elicits various organ-specific immune responses. Although advanced hepatocellular carcinoma (aHCC) showed 20–40% objective response rates (ORR) for cases of extrahepatic lesions in sites such as the lungs or lymph nodes (LNs), only 10% of intrahepatic lesions responded to the monotherapy. The organ-specific responses were due to tumor heterogeneity and differential microenvironments, and may have contributed to the failure of the phase III trials of anti-PD-1 monotherapy for aHCC. Recently, the combination of atezolizumab and bevacizumab (Ate/Bev) as first-line systemic treatment has resulted in survival benefits for patients with aHCC. However, the organ-specific response for this treatment has not been explored. We aimed to evaluate the organ-specific response to Ate/Bev combination therapy in patients with aHCC. Methods: We enrolled patients who received first-line Ate/Bev treatment for aHCC. Eligible patients included those with Child-Pugh A liver function, measurable tumor lesions, and serial image studies available for response evaluation. An independent radiologist reviewed the tumors located in the liver, lungs, LNs, and other sites. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used. Results: Between May 2020 and June 2021, 124 patients from two Korean cancer referral institutions received first-line Ate/Bev treatment for aHCC. The patient baseline characteristics included: hepatitis B (n = 85, 68.5%), hepatitis C (n = 6, 4.8%), non-viral (n = 33, 26.7%); BCLC stage A/B/C (n = 2, 1.6%/n = 19, 15.3%/n = 103, 83.1%); macrovascular invasion (n = 39, 31.5%); extrahepatic metastasis (n = 75, 60.5%); and AFP >400 ng/ml (n = 39, 31.5%). The median age was 62 years (range: 34–90). With median follow-up duration of 10.1 months, median progression-free survival was 6.8 months (95% CI, 3.6–10.0) and median overall survival was 16.9 months (95% CI, range not available). The ORR was 29.8%. For 260 individual tumor lesions, the liver was the most commonly involved organ (n = 152, 58.5%), followed by the LNs (n = 42, 16.2%) and lungs (n = 24, 9.2%). Ate/Bev treatment induced potent tumor shrinkage in both intrahepatic and extrahepatic lesions: ORR for hepatic lesions was 28.3%; LN lesions, 40.5%; lung lesions, 29.1%; and other metastatic lesions, 19.0%. Further, the organ-specific response rate for intrahepatic tumors decreased as the tumor size increased (36.7%: ≤50 mm, 13.0%: >50 mm). Conclusions: Unlike anti-PD-1 monotherapy, Ate/Bev combination therapy showed favorable responses even in intrahepatic lesions, which are comparable to those in extrahepatic lesions. As such, Ate/Bev may overcome an immune-tolerant hepatic microenvironment in patients with aHCC. (NCT04862949).