Redefining first-line standards with new partners
Affiliations & Notes
aDivision of Medical Oncology, National Cancer Centre Singapore, Singapore
bDepartment of Medical Oncology, Thoracic Group, Gustave Roussy, Villejuif 94805, France
cDepartment of Medicine, Paris–Saclay University, Paris, France
Article Info
Publication History:
Published May 29, 2026
DOI: 10.1016/S0140-6736(26)01038-X External LinkAlso available on ScienceDirect External Link
Copyright: © 2026 Published by Elsevier Ltd.
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OkAlthough antibody-drug conjugates (ADCs) have been touted as potential drugs or agents in the treatment of non-small-cell lung cancer (NSCLC), two randomised phase 3 trials evaluating the TROP2 ADCs datopotamab deruxtecan1 and sacituzumab govitecan2 did not show a significant survival benefit when compared with second-line docetaxel. Despite these initial disappointments, the ability of ADCs to modulate the tumour microenvironment has piqued interest in combining these agents with immune checkpoint inhibitors (ICIs).3 Early data from phase 2 studies conducted in the first-line setting suggested a potential increase in toxicities with this combination, and efficacy signals appeared moderate when contextualised against pivotal phase 3 chemoimmunotherapy trials.4–6 Nevertheless, the promise of biological synergism has already led to the enrolment of at least 8000 patients in ten ongoing phase 3 first-line trials for advanced wild-type NSCLC evaluating ADC-ICI with or without chemotherapy.
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