Characteristics and Prognosis of Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab/Bevacizumab Combination Therapy Who Achieved Complete Response

Abstract

Aim: To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Methods: A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child-Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients.

Results: The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well.

Conclusions: Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.

Keywords: atezolizumab; bevacizumab; cancer-free; complete response; drug-off; hepatocellular carcinoma; transarterial chemoembolization.

Figure 1

PFS and OS of Atz/Bev alone for all 120 patients stratified by the best antitumor response according to mRECIST. (a) Median PFS was 19.3 months (95%CI: 12.6 months–NR) for the CR group, 14.5 months (95%CI: 10.3–16.7) for the PR group, 6.9 months (95%CI: 4.1–9.2 months) for the SD group, and 1.4 months (95%CI: 1.4–1.4 months) for the PD + NE group. (b) Median OS was NR (95%CI: 21.0 months–NR) for the CR group, 24.5 months (95%CI: 21.1 months–NR) for the PR group, 26.4 months (95%CI: 12.2 months–NR) for the SD group, and 6.8 months (95%CI: 5.1–9.1 months) for the PD + NE group. PFS, progression-free survival; OS, overall survival; Atz/Bev, atezolizumab/bevacizumab; mRECIST, modified Response Evaluation Criteria in Solid Tumors; CI, confidence interval; NR, not reached; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not evaluated; M, months.

Figure 2

PFS and OS of Atz/Bev + additional TACE for all 120 patients in the CR and non-CR groups according to mRECIST. (a) Median PFS in the CR group (n = 24) was 19.3 months (95%CI: 15.4–26.4 months), significantly longer than the 6.9 months (95%CI: 3.7–9.0 months) in the non-CR group (n = 96) (p < 0.0001). (b) Median OS in the CR group was not reached (95%CI: 21.1 months–NR), significantly longer than the 19.3 months (95%CI: 13.6–26.4 months) in the non-CR group (p < 0.0001). PFS, progression-free survival; OS, overall survival; Atz/Bev, atezolizumab/bevacizumab; TACE, transarterial chemoembolization; CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; CI, confidence interval; NR, not reached; M, months.

Figure 3

Time to CR by mRECIST and duration of CR by mRECIST in patients who achieved CR by Atz/Bev alone (n = 18). (a) Median time to CR by mRECIST was 3.4 months (95%CI: 3.4–4.4 months). (b) Duration of CR by mRECIST was 15.6 months (95%CI: 7.1 months–NR). (c) Median CR duration for the drug-free group (n = 10) was 23.0 months (95%CI: 5.7 months–NR months) and for the non-drug-free group (n = 8) was 15.6 months (95%CI: 6.9 months–NR), with no significant difference between the groups (p = 0.584). CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; Atz/Bev, atezolizumab/bevacizumab; CI, confidence interval.

Figure 4

Clinical outcomes in patients who achieved CR by mRECIST—stratified by drug-free status. CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; Atz/Bev, atezolizumab/bevacizumab; PD, progressive disease; TACE, transarterial chemoembolization.