Antibody-drug conjugates in lung and breast cancer: current evidence and future directions-a position statement from the ETOP IBCSG Partners Foundation.

Details

Serval ID
serval:BIB_A510AA983B34
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibody-drug conjugates in lung and breast cancer: current evidence and future directions-a position statement from the ETOP IBCSG Partners Foundation.
Journal
Annals of oncology
Author(s)
Peters S., Loi S., André F., Chandarlapaty S., Felip E., Finn S.P., Jänne P.A., Kerr K.M., Munzone E., Passaro A., Pérol M., Smit E.F., Swanton C., Viale G., Stahel R.A.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
07/2024
Peer-reviewed
Oui
Volume
35
Number
7
Pages
607-629
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
Following the approval of the first antibody-drug conjugates (ADCs) in the early 2000s, development has increased dramatically, with 14 ADCs now approved and >100 in clinical development. In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small-cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 [datopotamab deruxtecan and sacituzumab govitecan (SG)] and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing. Thus, in the coming years, we are likely to see significant changes to treatment algorithms. As the number of available ADCs increases, biomarkers (of response and resistance) to better select patients are urgently needed. Biopsy sample collection at the time of treatment selection and incorporation of translational research into clinical trial designs are therefore critical. Biopsy samples taken peri- and post-ADC treatment combined with functional genomics screens could provide insights into response/resistance mechanisms as well as the impact of ADCs on tumour biology and the tumour microenvironment, which could improve understanding of the mechanisms underlying these complex molecules. Many ADCs are undergoing evaluation as combination therapy, but a high bar should be set to progress clinical evaluation of any ADC-based combination, particularly considering the high cost and potential toxicity implications. Efforts to optimise ADC dosing/duration, sequencing and the potential for ADC rechallenge are also important, especially considering sustainability aspects. The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access to data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.
Keywords
Humans, Immunoconjugates/therapeutic use, Immunoconjugates/pharmacology, Lung Neoplasms/drug therapy, Lung Neoplasms/pathology, Lung Neoplasms/genetics, Breast Neoplasms/drug therapy, Breast Neoplasms/pathology, Breast Neoplasms/genetics, Female, Antineoplastic Agents, Immunological/therapeutic use, Antineoplastic Agents, Immunological/pharmacology, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/pathology, Carcinoma, Non-Small-Cell Lung/genetics, antibody–drug conjugate, biomarkers, breast cancer, lung cancer, research priorities, resistance
Pubmed
Create date
29/04/2024 9:01
Last modification date
29/06/2024 8:30
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