Evaluation of Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma Using the Combination of Response Evaluation Criteria in Solid Tumors and Alpha-Fetoprotein

Abstract

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child-Pugh Score of 5-7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Keywords: Response Evaluation Criteria in Solid Tumors (RECIST); alpha-fetoprotein (AFP); atezolizumab plus bevacizumab combination therapy (Atezo + Beva); hepatocellular carcinoma (HCC); overall survival (OS); progression-free survival (PFS).

Figure 1

Overall survival (OS) and progression-free survival (PFS) from the initiation of atezolizumab plus bevacizumab (Atezo + Beva) in the 109 patients included in this study. (a) OS from the initiation of Atezo + Beva (median survival time (MST), 21.0 months). (b) PFS from the initiation of Atezo + Beva (median, 9.5 months).

Figure 2

Comparison of overall survival (OS) and progression-free survival (PFS) by radiological response at the first, second, and best response evaluations by Response Evaluation Criteria in Solid Tumors (RECIST). (a) OS at the first response (objective response (OR) not-reached, SD 21.0 months, PD 16.8 months, p = 0.15). (b) OS at the second response (OR not-reached, SD 20.6 months, PD 16.8 months, p = 0.003). (c) OS at the best response (OR not-reached, SD 20.6 months, PD 11.5 months, p < 0.001). (d) PFS at the first response (OR 10.7 months, SD 10.5 months, p = 0.70). (e) PFS at the second response (OR 14.7 months, SD 10.5 months, p = 0.052). (f) PFS at the best response (OR 16.6 months, SD 8.2 months, p < 0.001).

Figure 3

Comparison of overall survival (OS) between the group with a 25% or greater increase in AFP values at the first radiological response evaluation from Atezo + Beva initiation and the other group in 71 patients with SD at the first radiological response evaluation by Response Evaluation Criteria in Solid Tumors (25% or greater increase in AFP value 11.1 months, other group 21.0 months, p = 0.024).