Systematic review of the CUP trials characteristics and perspectives for next-generation studies.

Cancer of unknown primary Immunotherapy Site-specific therapy Targeted therapy

Journal

Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030

Informations de publication

Date de publication:
Jun 2022
Historique:
received: 01 03 2022
revised: 30 04 2022
accepted: 03 05 2022
pubmed: 16 5 2022
medline: 25 5 2022
entrez: 15 5 2022
Statut: ppublish

Résumé

Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients. Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials. Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses. Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.

Sections du résumé

BACKGROUND BACKGROUND
Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients.
METHODS METHODS
Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials.
FINDINGS RESULTS
Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses.
CONCLUSION CONCLUSIONS
Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.

Identifiants

pubmed: 35569387
pii: S0305-7372(22)00071-8
doi: 10.1016/j.ctrv.2022.102407
pii:
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0

Types de publication

Journal Article Review Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

102407

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Auteurs

Elie Rassy (E)

Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: elie.rassy@hotmail.com.

Chris Labaki (C)

Dana Farber Cancer Institute, Boston, USA.

Roy Chebel (R)

University of Wisconsin-Madison, Wisconsin, USA.

Stergios Boussios (S)

King's College London, Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, SE1 9RT London, UK.

Julie Smith-Gagen (J)

School of Public Health, University of Nevada, Reno, NV, USA.

F Anthony Greco (FA)

Sarah Cannon Cancer Center and Research Institute, Tennessee Oncology, Nashville, TN, USA.

Nicholas Pavlidis (N)

University of Ioannina, Ioannina, Greece.

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Classifications MeSH