Evidence map›Paper›PMID 36923309›Full record

Trial reportCancer research communications2022

Repurposing Azacitidine and Carboplatin to Prime Immune Checkpoint Blockade-resistant Melanoma for Anti-PD-L1 Rechallenge.

Andre van der Westhuizen, Megan Lyle, Moira C Graves, Xiaoqiang Zhu, Jason W H Wong, Kerrie Cornall, Shu Ren, Leanna Pugliese, Richard Levy, Adeeb Majid and 2 more

Open access · goldFull text readClinical Trial, Phase II
In one paragraph

Trial report in Cancer research communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

7 citing papers in PubMed, 4 citations in OpenAlex.

  1. Current clinical applications and future developments of platinum-based anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026
    Review
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  4. Article
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  7. Plants (Basel, Switzerland) · 2025
    Article
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

12 authors at 5 institutions in 2 countries.

Andre van der WesthuizenHunter Medical Research Institute and School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.
Megan LyleLiz Plummer Cancer Centre, Cairns Hospital, Cairns, Queensland, Australia.
Moira C GravesHunter Medical Research Institute and School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.ORCID 0000-0002-3380-5417
Xiaoqiang ZhuSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, P.R. China.
Jason W H WongSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, P.R. China.ORCID 0000-0003-2953-7728
Kerrie CornallDepartment of Medical Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia.
Shu RenDepartment of Medical Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia.
Leanna PuglieseDepartment of Medical Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia.
Richard LevyDepartment of Surgery, Calvary Mater Hospital, Newcastle, NSW, Australia.
Adeeb MajidDepartment of Surgery, Calvary Mater Hospital, Newcastle, NSW, Australia.ORCID 0000-0002-5361-1708
Ricardo E VilainHunter Medical Research Institute and School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.
Nikola A BowdenHunter Medical Research Institute and School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.ORCID 0000-0002-6047-1694
Calvary Mater Newcastle Hospital · AUCity University of Hong Kong · HKUniversity of Newcastle Australia · AUCairns Hospital · AUNew South Wales Department of Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Drug repurposing offers the opportunity for chemotherapy to be used to reestablish sensitivity to immune checkpoint blockade (ICB) therapy. Here we investigated the clinical and translational aspects of an early phase II study of azacitidine and carboplatin priming for anti-PDL1 immunotherapy (avelumab) in patients with advanced ICB-resistant melanoma. Experimental Design: A total of 20 participants with ICB-resistant metastatic melanoma received 2 × 4-week cycles of azacitidine and carboplatin followed by ICB rechallenge with anti-PD-L1 avelumab. The primary objective was overall response rate after priming and ICB rechallenge. Secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Translational correlation analysis of HLA-A and PD-L1 expression, RNA sequencing, and reduced representation bisulfite sequencing of biopsies at baseline, after priming and after six cycles of avelmuab was performed. Results: The overall response rate (ORR) determined after azacitidine and carboplatin priming was 10% (2/20) with two partial responses (PR). The ORR determined after priming followed by six cycles of avelumab (week 22) was 10%, with 2 of 20 participants achieving immune partial response (iPR). The CBR for azacitidine and carboplatin priming was 65% (13/20) and after priming followed by six cycles of avelumab CBR was 35% ( Conclusions: Priming with azacitidine and carboplatin can induce disease stabilization and resensitization to ICB for metastatic melanoma. Significance: There are limited treatments for melanoma once resistance to ICB occurs. Chemotherapy induces immune-related responses and may be repurposed to reinstate the response to ICB. This study provides the first evidence that chemotherapy can provide clinical benefit and increase OS for ICB-resistant melanoma.

Indexed as

AzacitidineCarboplatinDrug RepositioningDrug Resistance, NeoplasmImmune Checkpoint InhibitorsMelanomaAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkersDNA DamageDNA MethylationEpigenesis, GeneticFemaleAntibodies, Monoclonal, HumanizedavelumabAzacitidineB7-H1 AntigenBiomarkersCarboplatinCD274 protein, humanHLA-A AntigensImmune Checkpoint Inhibitors

Identifiers

PMID36923309
PMCPMC10010343
OpenAlexW4288715299

What OpenQuestion holds

Textfull text, public
LicenceCC BY
reference markers read1
measurements read106
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.