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. 2024 Jul 1;7(7):e2423390.
doi: 10.1001/jamanetworkopen.2024.23390.

Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023

Marco Mariani  1   2 , Giulia Viale  1   2 , Barbara Galbardi  2 , Luca Licata  1   2 , Carlo Bosi  1   2 , Matteo Dugo  2 , Giulia Notini  1   2 , Matteo M Naldini  1   2 , Maurizio Callari  3 , Carmen Criscitiello  4   5 , Lajos Pusztai  6 , Giampaolo Bianchini  1   2
Affiliations

Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023

Marco Mariani et al. JAMA Netw Open. .

Abstract

Importance: Clinical trials are the path to test and introduce new therapies in the clinic. Trials that are unable to produce results represent inefficiency in the system and may also undermine patient confidence in the new drug development process.

Objectives: To survey the immunotherapy clinical trial landscape of breast cancer between January 2004 and April 2023 and examine what fraction of trials with primary completion date up to November 30, 2022, failed to report outcome, assessing the proportion of trials that yielded positive results and describing trial features associated with these 2 outcomes.

Design, setting, and participants: This cross-sectional study included breast cancer immunotherapy trials identified in ClinicalTrials.gov. Trial details and results were retrieved in December 2023. Google Scholar, PubMed, and LARVOL CLIN websites were also searched for reports.

Main outcomes and measures: Trial outcome reported as abstract or manuscript. Reported trials were categorized as positive (ie, met its end point) or negative. Association between reporting and trial features were tested using Fisher exact test.

Results: A total of 331 immuno-oncology trials were initiated in breast cancer by April 2023; 242 trials were phase II, 47 were phase I, and 42 phase III. By setting, 212 studies (64.0%) were conducted in metastatic, 94 (28.4%) in neoadjuvant, and 25 (7.6%) in adjuvant settings. Among phase II and III trials, 168 (59.2%) were nonrandomized. One hundred twenty trials had primary completion dates up to November 30, 2022, of which 30 (25.0%; enrolling a combined 2428 patients) failed to report their outcomes; 7 phase I trials (31.8%), 21 phase II trials (23.6%), and 2 phase III trials (22.2%) were unreported. Single-center studies were significantly more likely to be unreported than multicenter studies (19 of 54 [35.2%] vs 9 of 60 [15.0%]; P = .02). Of the 90 reported trials, 47 (52.2%) and 43 (47.8%) were positive and negative, respectively. Seventeen of 19 (89.5%) of the reported randomized trials (accruing a total of 4189 patients) were negative.

Conclusions and relevance: In this cross-sectional study of immunotherapy breast cancer trials, the large number of trials yielded modest clinical impact. Single-center trials commonly failed to report their outcomes and many phase II studies have not translated into corresponding successful phase III trials.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Viale reported personal fees from serving on advisory boards for Gilead, speaking fees from Pfizer and Eli Lilly, and travel fees from Eli Lilly and Pfizer outside the submitted work. Dr Licata reported service on advisory boards for Eli Lilly, Exact Sciences, AstraZeneca, Italfarmaco, Daiichi Sankyo, Accord, Seagen; he reported receiving consulting fees from Exact Sciences, Helsinn, EISAI, and Daiichi Sankyo; he received speaker fees from Gilead, Exact Sciences, Helsinn, and Eli Lilly; and he received travel fees Eli Lilly, Gilead, and Accord outside the submitted work. Dr Bosi reported receiving consulting fees from Kardo Srl; he reported travel support, accommodations, and expenses from Gilead, Daichii-Sankyo, and Eli Lilly. Dr Criscitiello reported receiving grants from Gilead and Seagen outside the submitted work; she reported consulting and/or speaking fees from MSD, Daiichi Sankyo, AstraZeneca, Roche, Novartis, Eli Lilly, and Pfizer outside the submitted work. Dr Pusztai reported receiving consulting fees and honoraria for advisory board participation from Pfizer, Astra Zeneca, Merck, Novartis, Bristol-Myers Squibb, Stemline-Menarini, GlaxoSmithKline, Genentech/Roche, Personalis, Daiichi, Natera, Agendia, and Exact Sciences and institutional research funding from Seagen, GlaxoSmithKline, AstraZeneca, Merck, Pfizer, and Bristol Myers Squibb outside the submitted work. Dr Bianchini reported receiving grants from Gilead outside the submitted work; he reported receiving personal fees from Roche, AstraZeneca, Daiichi Sankyo, MSD, Eli Lilly, Pfizer, Novartis, EISAI, Exact Science, Gilead, Seagen, Menarini/Stemline, and Agendia; he reported receiving nonfinancial support from Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, and Gilead outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overview of Immuno-Oncology Trials in Breast Cancer Opened Between 2004 and April 2023
Multiple way combination describes immunotherapy combined with several drugs with different mechanisms of action.
Figure 2.
Figure 2.. Landscape of Anti-PD-1 and Anti-PD-L1 Combination Trials in Breast Cancers
CSF-1R indicates colony-stimulating factor-1 receptor; EGFR, epidermal growth factor receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GnRH, gonadotropin hormone-releasing hormone; IL, interleukin; IORT, intraoperative radiation therapy; PARP, poly (adenosine diphosphate–ribose) polymerase; PD-1, programmed cell death protein 1; PD-L1, programmed death ligand 1; T-DM1, trastuzumab emtansine; TGFb, transforming growth factor-β; TKI, tyrosine kinase inhibitor; VEGFR-2, vascular endothelial growth factor; VRP, virus replicon particle.
Figure 3.
Figure 3.. Evolution of Types of Immunotherapy Trials in Breast Cancer
Updated as of December 31, 2022. Multiple way combination describes immunotherapy combined with several drugs with different mechanisms of action.
See this image and copyright information in PMC

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