Safety of combining radiotherapy and antibody drug conjugates in advanced urothelial and other cancers.
Authors: Derrick Lock, Yash Soni, Lindsay Hwang, Suzanne Cole, Anishka D'souza, Aurelie Garant, Daniel X. Yang, Waddah Arafat, Tian Zhang, Leslie K. Ballas, Neil B Desai
Journal: Journal of Clinical Oncology (2025)

758 Background: Antibody drug conjugates (ADCs) such as enfortumab vedotin (EV) and sacituzumab govitecan (SG) are novel treatments increasingly used for metastatic urothelial carcinoma (mUC). SG is also utilized in metastatic breast cancer (mBC). Radiotherapy (RT) is used for palliation or consolidation of metastatic sites in mUC and for bladder preservation in localized disease. There is limited data evaluating the safety of ADCs when combined with RT. We sought to characterize the safety of RT in patients with mUC or mBC cancer receiving EV or SG. Methods: A bi-institutional retrospective analysis was performed. Eligible patients had a diagnosis of mUC or mBC and received RT within 6 months of EV or SG receipt. Patients were stratified by intensity of RT (higher vs. lower), site of RT (pelvis with bladder, pelvis without bladder, outside pelvis), and RT timing relative to ADC (prior to, within 4 weeks of, or after ADC infusion). ADC status was categorized as discontinued for progression of disease, discontinued for toxicity, or continued therapy. Those who discontinued ADC for toxicity were further evaluated to assess attribution to RT vs. expected treatment-limited toxicity of ADC. Results: Between January 1, 2020 and January 31, 2024, 103 patients received 166 RT courses within 6 months of ADC. RT courses were of mostly lower intensity (66%) vs. higher intensity (34%), using a cutoff of biologically equivalent dose (a/b=10) of 35Gy after assessing the distribution of RT regimens. RT location was extra-pelvic (58%), pelvis without bladder (16%), brain (14%), and pelvis with bladder (11%). RT delivery occurred prior to ADC (30%), concurrent with ADC (46%), or after ADC completion (24%). Of 77 RT courses concurrent with ADC, 10 (13%) patients experienced grade 3-5 toxicity. All of these were attributed to known ADC toxicities and only one possibly influenced by addition of RT. No patients receiving RT to the bladder experienced high-grade toxicity. Conclusions: This real world, retrospective study thus found no added safety events for patients receiving RT with ADCs, even when administered concurrently. Further data to validate these findings is needed as the use of both ADCs and RT increases in patients with urothelial carcinoma. Concurrent ADC–RT and toxicity. Patient # Toxicity Grade Toxicity History Relationship to RT 1 G3 skin Out of RT field Unlikely 2 G3 neuropathy Out of RT field Unlikely 3 G3 neuropathy Out of RT field Unlikely 4 G3 neuropathy Out of RT field Unlikely 5 G3 neuropathy Out of RT field Unlikely 6 G3 pneumonitis Out of RT field Unlikely 7 G3 skin Out of RT field Unlikely 8 G3 thrombocytopenia Began prior to RT Unlikely 9 G3 oral mucositis Out of RT field Unlikely 10 G5 neutropenia vs. pneumonitis 1 week after completing craniospinal irradiation, ADC infusions resumed; two weeks later, the patient was admitted for pneumonia Possible ADC: Antibody-drug conjugate; RT: Radiotherapy.