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Reporting of older subgroups in registration breast cancer trials 2012–2021

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Abstract

Introduction

Adequate reporting of data specific to older populations enrolled to breast cancer trials is critical, given the high incidence of the disease among this demographic. This study aimed to examine the completeness of reporting of older subgroups among patients recruited to registration clinical trials investigating systemic treatments for breast cancer.

Methods

Clinical trials leading to a US food and drug administration (FDA) approval in breast cancer between 2012 and 2021 were included. Primary study reports and and all available secondary publications were systematically and objectively assessed with regard to the availability of data regarding efficacy, baseline characteristics, safety, and health-related quality of life (HRQOL) outcomes among older subgroups.

Results

27 trials and 216 publications were assessed. 20.3% of patients were aged ≥65. 70.0% of patients had an eastern cooperative oncology group (ECOG) performance status of 0. Although complete reporting of primary endpoints was adequate (72.7%), most protocol-defined primary endpoints were surrogate endpoints (84.8%). Overall survival data among older populations was unavailable in 50.0% of studies. Reporting was poor for secondary efficacy endpoints (81.8% unreported), baseline characteristics (70.4% unreported), toxicity (55.6% unreported), and health-related quality of life outcomes (87.5% unreported).

Conclusion

The findings underline significant deficits in the reporting of age-specific data in breast cancer registration trials. The underreporting of key efficacy, safety, and HRQOL outcomes highlights the need for mandatory reporting standards and a dedicated emphasis on older populations' priorities and needs in the reporting of registration clinical trials.

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Data avavilability

A list of publications reviewed is included in the supplementary materials. Further data used in conducting analyses are available from the corresponding author upon reasonable request.

Abbreviations

ASCO:

American society of clinical oncology

BCS:

Breast-conserving surgery

CBR:

Clinical benefit rate

CDK4/6:

Cyclin-dependent kinase 4/6

CNS Int:

Time to central nervous system intervention

CNS Rec:

Central nervous system recurrence

CRR:

Clinical response rate

DCR:

Disease control rate

DDFS:

Distant disease-free survival

DFS:

Disease-free survival

DOR:

Duration of response

DRFI:

Distant recurrence-free interval

DRFS:

Distant recurrence-free survival

ECOG PS:

Eastern cooperative oncology group performance status

EFS:

Event-free survival

EORTC QLQ-ELD14:

European organisation for research and treatment of cancer quality of life questionnaire elderly module 14

ER:

Estrogen receptor

FDA:

Food and drug administration

HER2:

Human epidermal growth factor receptor 2

HRQOL:

Health-related quality of life

IDFS:

Invasive disease-free survival

mTOR:

Mammalian target of rapamycin

ORR:

Objective response rate

OS:

Overall survival

pCR:

Pathological complete response

PFS:

Progression-free survival

PFS2:

Second progression-free survival

PIK3CA:

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

PUBMED:

PubMed database

RFI:

Relapse-free interval

SLD%:

Percentage change in sum of longest diameters

TTDR:

Time to distant recurrence

TTF:

Time to treatment failure

TTR:

Time to response

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Funding

Funding was not sought for this publication.

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Authors and Affiliations

  1. Breast Cancer Unit, Royal Marsden Hospital, Sutton, London, UK

    Colm Mac Eochagain & Nicolò Matteo Luca Battisti

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  1. Colm Mac Eochagain
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  2. Nicolò Matteo Luca Battisti
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Contributions

Conceptualization: CME. Methodology: CME, NB. Data Collection: CME. Data Analysis: CME, NB. Statistical Analysis: CME. Writing—Original Draft: CME, NB. Writing—Review & Editing: CME, NB.

Corresponding author

Correspondence to Colm Mac Eochagain.

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Conflicts of interest

CME declares no conflicts of interest related to this study. NB reports the following conflicts of interest: Advisory board: Pfizer, Abbott, Sanofi, Astellas. Travel grants: Exact Sciences, Pfizer, Lilly, Novartis. Speaker fees: Pfizer, AbbVie, Roche, Sanofi, Novartis, Servier, Gilead, AstraZeneca.

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This study is an analysis of previously published data and did not require additional ethical approval.

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Eochagain, C.M., Battisti, N.M.L. Reporting of older subgroups in registration breast cancer trials 2012–2021. Breast Cancer Res Treat 202, 411–421 (2023). https://doi.org/10.1007/s10549-023-07081-0

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