ESMO E-Learning: Advances and Challenges in Antibody-Drug Conjugates: A Multi-Tumour Perspective

Antibody-drug conjugates (ADCs) represent a robust precision-guided, payload-delivering vehicle as anticancer therapeutics. In this E-Learning module, the authors provide an overview of their efficacy from the clinical trials, testing the ADCs in patients with advanced breast cancer, bladder cancer, non-small cell lung cancer (NSCLC), gastrointestinal cancers, ADC-related toxicity profile and guidance for toxicity management, the current status of approvals and future outlook in ADC development.

The module starts with the presentation  of ado-trastuzumab emtansine, the first ADC approved for patients with HER2-positive breast cancer. It goes on to elaborate on trastuzumab deruxtecan in HER2-positive, HER2-low and HER2-ultralow settings. This is followed by an overview of the toxicity profile and guidance for toxicity management. The next chapter on breast cancer is dedicated to an overview of efficacy and adverse events of sacituzumab govitecan, followed by an overview of datopotamab deruxtecan and multiple ADCs currently in development. The module also elaborates on how to sequence different ADCs, implications of resistance mechanisms for ADC sequencing and on how the field is moving forward, including the combination therapy.

The chapter dedicated to ADCs in bladder cancer, covers, in terms of approved drugs, enfortumab vedotin, alone or with pembrolizumab, as well as sacituzumab govitecan, and in terms of ADCs currently in clinical trials, it elaborates on disitimab vedotin alone or with pembrolizumab.

It is stated that trastuzumab deruxtecan is currently approved by the FDA for HER2 exon 20 insertion NSCLC and HER2 3+ by immunohistochemistry, while a plethora of ADCs in clinical trials for NSCLC, not yet the standard-of-care, are covered in terms of efficacy and safety for the remainder of the module.

The last part of the module elaborates on ADCs for gastrointestinal cancers, namely gastric, colorectal and hepatobiliary cancers.