Abstract 5459: Association between stomatitis and treatment efficacy with novel TROP2-directed antibody drug conjugate (ADC), datopotamab deruxtecan, in patients with metastatic cancer
Authors: Abelman Rachel O. , Spring Laura M. , Ryan Phoebe K. , Fell Geoffrey , Juric Dejan , Heist Rebecca S. , Bardia Aditya 
Published: June 2023

Abstract
Background: Incidence of toxicity with immunotherapy has been correlated with likelihood of treatment response (Hussaini, Cancer Treat Rev 2021; Schuell, Br J Cancer 2005). However, this phenomenon has not yet been demonstrated with antibody-drug conjugates. Datopotamab deruxtecan (Dato-DXd) is a novel ADC composed of an anti-Trop2 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase-I inhibitor payload (Bardia, Annals of Onc 2021). Early phase studies have demonstrated significant activity in heavily pretreated patients with metastatic non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). Stomatitis was a common treatment-emergent adverse event (TEAE) observed in clinical trials. We conducted a study to evaluate the association between incidence of stomatitis and treatment response with Dato-DXd and evaluate the impact of steroid mouthwash. We hypothesized that presence and grade of mucositis would correlate with observed treatment efficacy.
Methods: We included all patients treated at one academic institution (Massachusetts General Hospital) with Dato-DXd. Stomatitis was assessed by NCI-CTCAE V5.0. Objective Response Rate (ORR) was assessed by RECIST criteria with independent radiology review. Use of mouthwash was evaluated by secondary review and categorized as primary or secondary prophylaxis. A time-to-event analysis was performed to evaluate the time to onset of stomatitis.
Results: 60 patients, including 19 with MBC and 41 with NSCLC, were treated with Dato-DXd between June 2018-September 2022. The median age of patients was 64 and 41/60 patients were female. The median time to onset of mucositis was 14 days (95% CI 12-42 days). There was no significant difference in incidence of stomatitis between the MBC and NSCLC cohorts. Compared to patients who had progressive disease (PD), patients who had a partial response (PR) or stable disease (SD) were 11 times more likely to have stomatitis (OR 11.0, 95% CI 3.61-44.01, p&lt;0.001). Later in the trial (January 2020 onward), 28 patients received primary steroid prophylaxis - excluding these patients, those who were found to have PR/SD were 8.8 times more likely to develop stomatitis compared to patients who had PD (OR 8.8, 95% CI 1.5-73.3, p=0.023).
Conclusion: The development of stomatitis may be associated with higher likelihood of therapeutic efficacy. Given that these findings are a hypothesis-generating post-hoc exploratory analysis from a single institution, this requires validation in larger studies before drawing strong conclusions and impacting clinical decision making. Further research is also needed evaluate the relationship between TEAEs and therapeutic efficacy with other ADCs.
Citation Format: Rachel O. Abelman, Laura M. Spring, Phoebe K. Ryan, Geoffrey Fell, Dejan Juric, Rebecca S. Heist, Aditya Bardia. Association between stomatitis and treatment efficacy with novel TROP2-directed antibody drug conjugate (ADC), datopotamab deruxtecan, in patients with metastatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5459.