Skip to main content

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.

Publication ,  Journal Article
Nayak, L; Molinaro, AM; Peters, K; Clarke, JL; Jordan, JT; de Groot, J; Nghiemphu, L; Kaley, T; Colman, H; McCluskey, C; Gaffey, S; Smith, TR ...
Published in: Clin Cancer Res
February 15, 2021

PURPOSE: VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma. PATIENTS AND METHODS: Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, n = 50) or pembrolizumab monotherapy (cohort B, n = 30). The primary endpoint was 6-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor programmed death-ligand 1 expression, tumor-infiltrating lymphocyte density, immune activation gene expression signature, and plasma cytokines. The neurologic assessment in neuro-oncology (NANO) scale was used to prospectively assess neurologic function. RESULTS: Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3-41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7-14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7-25.4), median OS was 10.3 months (95% CI, 8.5-12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant IDH1, unmethylated MGMT, and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment. CONCLUSIONS: Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

February 15, 2021

Volume

27

Issue

4

Start / End Page

1048 / 1057

Location

United States

Related Subject Headings

  • Prospective Studies
  • Progression-Free Survival
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans
  • Glioblastoma
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nayak, L., Molinaro, A. M., Peters, K., Clarke, J. L., Jordan, J. T., de Groot, J., … Reardon, D. A. (2021). Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res, 27(4), 1048–1057. https://doi.org/10.1158/1078-0432.CCR-20-2500
Nayak, Lakshmi, Annette M. Molinaro, Katherine Peters, Jennifer L. Clarke, Justin T. Jordan, John de Groot, Leia Nghiemphu, et al. “Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.Clin Cancer Res 27, no. 4 (February 15, 2021): 1048–57. https://doi.org/10.1158/1078-0432.CCR-20-2500.
Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, de Groot J, et al. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021 Feb 15;27(4):1048–57.
Nayak, Lakshmi, et al. “Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.Clin Cancer Res, vol. 27, no. 4, Feb. 2021, pp. 1048–57. Pubmed, doi:10.1158/1078-0432.CCR-20-2500.
Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, de Groot J, Nghiemphu L, Kaley T, Colman H, McCluskey C, Gaffey S, Smith TR, Cote DJ, Severgnini M, Yearley JH, Zhao Q, Blumenschein WM, Duda DG, Muzikansky A, Jain RK, Wen PY, Reardon DA. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021 Feb 15;27(4):1048–1057.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

February 15, 2021

Volume

27

Issue

4

Start / End Page

1048 / 1057

Location

United States

Related Subject Headings

  • Prospective Studies
  • Progression-Free Survival
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Humans
  • Glioblastoma
  • Female