Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study

Clin Cancer Res. 2020 Nov 1;26(21):5631-5637. doi: 10.1158/1078-0432.CCR-20-0477. Epub 2020 Jul 28.

Abstract

Purpose: Atezolizumab has shown antitumor activity in patients with ovarian cancer. Dual blockade of programmed death-ligand 1 (PD-L1) and VEGF enhances anticancer immunity and augments antitumor activity in several cancers. The safety and efficacy of atezolizumab plus bevacizumab were evaluated in patients with ovarian cancer.

Patients and methods: In this open-label, multicenter phase Ib study, patients with platinum-resistant ovarian cancer received intravenous atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) once every 3 weeks. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory biomarkers were also evaluated.

Results: Twenty patients received treatment. Treatment-related adverse events occurred in 19 patients (95%); seven (35%) had grade 3/4 events. No grade 5 events occurred. The safety profile of atezolizumab plus bevacizumab was consistent with those of the individual agents. Two patients (10%) discontinued treatment because of pneumonitis and small bowel obstruction. Three patients had partial responses of 11.3-18.9 months' duration; the ORR was 15%. Eight patients (40%) had stable disease, hence the disease control rate was 55%. The median DOR was not reached (95% confidence interval, 11.3-not reached). Median PFS was 4.9 months (range, 1.2-20.2); median OS was 10.2 months (range, 1.2-26.6). No association was seen between treatment response and PD-L1 expression, tumor histology, or number of prior therapies.

Conclusions: Atezolizumab plus bevacizumab led to durable responses and/or disease stabilization in some patients with platinum-resistant ovarian cancer; the safety profiles were consistent with those of each agent.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Progression-Free Survival
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • atezolizumab