Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial

Cancer Med. 2021 Aug;10(16):5437-5447. doi: 10.1002/cam4.4090. Epub 2021 Jun 29.

Abstract

Background: IMbrave150 is a phase III trial that assessed atezolizumab + bevacizumab (ATEZO/BEV) versus sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (HCC) and demonstrated a significant improvement in clinical outcomes. Exploratory analyses characterized objective response rate (ORR), depth (DpR), and duration of response (DoR), and patients with a complete response (CR).

Methods: Patients were randomized 2:1 to intravenous ATEZO (1200 mg) + BEV (15 mg/kg) every 3 weeks or oral SOR (400 mg) twice daily. Tumors were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and HCC-modified RECIST (mRECIST). ORR by prior treatment and largest baseline liver lesion size, DoR, time to response (TTR), and complete response (TTCR) were analyzed.

Results: For both criteria, responses favored ATEZO/BEV versus SOR regardless of prior treatment and in patients with lesions ≥3 cm. Median TTR was 2.8 months per RECIST 1.1 (range: 1.2-12.3 months) and 2.8 months per mRECIST (range: 1.1-12.3 months) with ATEZO/BEV. Patients receiving ATEZO/BEV had a greater DpR, per both criteria, across baseline liver lesion sizes. Characteristics of complete responders were similar to those of the intent-to-treat population. In complete responders receiving ATEZO/BEV per mRECIST versus RECIST 1.1, respectively, median TTCR was shorter (5.5 vs. 7.0 months), mean baseline sum of lesion diameter was longer (5.0 [SD, 5.1] vs. 2.6 [SD, 1.4] cm), and mean largest liver lesion size was larger (4.8 [SD, 4.2] vs. 2.3 [SD, 1.0] cm).

Conclusions: These data highlight the improved ORR, DpR, and CR rates with ATEZO/BEV in unresectable HCC.

Trial registration: ClinicalTrials.gov NCT03434379.

Keywords: Response Evaluation Criteria in Solid Tumors; hepatocellular carcinoma; immunotherapy.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors
  • Sorafenib / administration & dosage*
  • Sorafenib / adverse effects
  • Tomography, X-Ray Computed

Substances

  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • atezolizumab
  • Sorafenib

Associated data

  • ClinicalTrials.gov/NCT03434379