ESMO Congress 2023
The place of antibody–drug conjugates in the evolving treatment landscape of solid tumors
Although the first ADC was approved 10 years ago, it has taken some time to regain the initial momentum and obtain more compelling data to mirror the enthusiasm around ADCs. The broad interest surrounding the topic of ADCs in the lead-up to ESMO 2023 was clear, with several widely anticipated data releases planned. The most prominent of these are highlighted below.
Bladder cancer
After two decades of platinum-based chemotherapy being standard of care in advanced bladder cancer, ESMO 2023 saw practice-changing results from the EV-302/KEYNOTE-A39 trial. Combination therapy of the nectin-4-directed ADC enfortumab vedotin with pembrolizumab almost doubled median PFS and OS versus chemotherapy in previously untreated, locally advanced or metastatic urothelial carcinoma.1 The excitement in the room was palpable, with the presentation receiving a standing ovation!
Cervical cancer
Hoping to change the treatment landscape for women with recurrent or metastatic cervical cancer, Vergote et al. presented their findings from the innovaTV 301/ENGOT-cx12/GOG-3057 study of tisotumab vedotin (TF-linked MMAE-targeted ADC) versus chemotherapy*. The results indicated that treatment with tisotumab vedotin lengthened survival and delayed relapse compared with chemotherapy, and led to tumor shrinkage more frequently than chemotherapy.2
Breast cancer
Promising results were also seen in the TROPION-Breast01 study assessing the TROP2-directed ADC datopotamab deruxtecan versus chemotherapy* in patients with inoperable or metastatic HR+, HER2− breast cancer who had previously received chemotherapy.3 In addition to showing that datopotamab deruxtecan has an encouraging safety profile, the study met its primary endpoint of significantly improved PFS, adding to the list of ADCs that are more effective than conventional chemotherapy.
The next key steps will be to refine optimal patient profiles for each ADC and determine the ideal treatment sequence to maximize outcomes.
*Investigator’s choice of chemotherapy.
ADC, antibody–drug conjugate; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MMAE, monomethyl auristatin E; OS, overall survival; PFS, progression-free survival; TF, tissue factor; TROP2, trophoblast cell surface antigen 2.
1. Powles TB et al. ESMO Congress 2023. Abstract LBA6; 2. Vergote B et al. ESMO Congress 2023. Abstract LBA9; 3. Bardia A et al. ESMO Congress 2023. AbstractLBA11.