Low baseline CXCL9 predicts early progressive disease in unresectable HCC with atezolizumab plus bevacizumab treatment

Autor: Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Liver Cancer (2022)
Druh dokumentu: article
ISSN: 2235-1795
1664-5553
DOI: 10.1159/000527759
Popis: Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, six weeks after treatment initiation (early PD; n = 13). Of these, four patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (< 333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs 227 days; HR: 2.41, 95% CI: 1.22–4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (< 333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
Databáze: Directory of Open Access Journals
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