Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants

Cancer Med. 2024 Jun;13(12):e7430. doi: 10.1002/cam4.7430.

Abstract

Aim: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs.

Methods: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed.

Results: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039).

Conclusions: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Keywords: atezolizumab and bevacizumab; bleeding event; combination immunotherapy; direct oral anticoagulant; hepatocellular carcinoma; lung cancer.

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Bevacizumab* / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Feasibility Studies*
  • Female
  • Hemorrhage* / chemically induced
  • Humans
  • Liver Neoplasms* / drug therapy
  • Lung Neoplasms* / drug therapy
  • Male
  • Middle Aged
  • Retrospective Studies

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab
  • Bevacizumab
  • Anticoagulants