Evidence map›Paper›PMID 33199490›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2021

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

Lakshmi Nayak, Annette M Molinaro, Katherine Peters, Jennifer L Clarke, Justin T Jordan, John de Groot, Leia Nghiemphu, Thomas Kaley, Howard Colman, Christine McCluskey and 12 more

Open access · bronzeAbstract readClinical Trial, Phase IIComparative StudyMulticenter Study
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
200citing papers in PubMed, 14 pooled it
16.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

200 citing papers in PubMed, 14 syntheses or guidelines pooled it, 246 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Anti-PD-1 and anti-PD-L1 antibodies for glioma.The Cochrane database of systematic reviews · 2025
    Pooled it
  4. Pooled it
  5. A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Trial
  16. Trial
  17. Trial
  18. Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  19. Review
  20. Review

140 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 10 institutions in 1 country.

Lakshmi NayakDana-Farber Cancer Institute, Boston, Massachusetts.
Annette M MolinaroUniversity of California San Francisco, San Francisco, California.
Katherine PetersDuke University Medical Center, Durham, North Carolina.
Jennifer L ClarkeUniversity of California San Francisco, San Francisco, California.ORCID 0000-0002-8054-7342
Justin T JordanMassachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-6198-817X
John de GrootM.D. Anderson Cancer Center, Houston, Texas.
Leia NghiemphuUniversity of California, Los Angeles, Los Angeles, California.
Thomas KaleyMemorial Sloan Kettering Cancer Center, New York City, New York.
Howard ColmanHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah.ORCID 0000-0002-4027-7317
Christine McCluskeyDana-Farber Cancer Institute, Boston, Massachusetts.
Sarah GaffeyDana-Farber Cancer Institute, Boston, Massachusetts.
Timothy R SmithBrigham and Women's Hospital, Boston, Massachusetts.
David J CoteBrigham and Women's Hospital, Boston, Massachusetts.
Mariano SevergniniDana-Farber Cancer Institute, Boston, Massachusetts.
Jennifer H YearleyMerck & Co., Inc., Kenilworth, New Jersey.
Qing ZhaoMerck & Co., Inc., Kenilworth, New Jersey.
Wendy M BlumenscheinMerck & Co., Inc., Kenilworth, New Jersey.
Dan G DudaMassachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-7065-8797
Alona MuzikanskyMassachusetts General Hospital, Boston, Massachusetts.
Rakesh K JainMassachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-7571-3548
Patrick Y WenDana-Farber Cancer Institute, Boston, Massachusetts.
David A ReardonDana-Farber Cancer Institute, Boston, Massachusetts. david_reardon@dfci.harvard.edu.
Dana-Farber Cancer Institute · USMassachusetts General Hospital · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USBrigham and Women's Hospital · USUniversity of California, San Francisco · USDuke Medical Center · USHuntsman Cancer Institute · USKettering University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Targeting 15-Prostaglandin Dehydrogenase (15-PGDH) in Cancer Risk, Prevention, and TreatmentR35CA197442 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2017 to 2023
$6.6M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
Reengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA208205NCI NIH HHS R35 CA197442NCI NIH HHS R35 CA197743
6 · The paper itself

Abstract

purposeVEGF 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

methodsEighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A,

resultsPembrolizumab 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

conclusionsPembrolizumab 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.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorBrain NeoplasmsDrug MonitoringFemaleGlioblastomaHumansMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisProgression-Free SurvivalAntibodies, Monoclonal, HumanizedBevacizumabBiomarkers, Tumorpembrolizumab

Identifiers

PMID33199490
PMCPMC8284901
OpenAlexW3099035428

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.