Abstract 289P
Background
Trastuzumab deruxtecan (T-DXd; DS-8201) is a HER2-targeted antibody drug conjugate with demonstrated antitumor activity and manageable safety profile in HER2-expressing/mutated solid tumors. Interstitial lung disease (ILD) is an important identified risk for patients (pts) treated with T-DXd. We report incidence of independently adjudicated drug-related ILD events and explore potential risk factors.
Methods
A post hoc analysis was conducted of pooled data from 542 pts who received at least one dose of 1.6, 3.2, 5.4, 6.4, 7.4, or 8.0 mg/kg T-DXd in two open-label interventional studies in advanced solid tumors (NCT02564900) and breast cancer (BC) (NCT03248492) (data cutoff, August 1, 2019). Baseline characteristics, exposure, incidence, and time to onset were summarized. Potential risk factors were evaluated in a stepwise multivariable logistic regression model.
Results
437 (80.6%) pts had BC; the remainder consisted of other tumors across all doses. 234 (43%) pts were from Japan. Median treatment duration was 8.4 months (range, 0.7-46.0). Overall, 16.8% (91/542) pts experienced an ILD (grade ≥ 3: 20/542, 3.7%), of which 18.1% (79/437) all grade ILD was reported in BC. Median time to onset was 208 days (range, 0-582) in the overall population and 134 days (range, 35-338) in the BC 5.4 mg/kg group. Potential risk factors associated with drug-related ILD were country (Japan vs. non-Japan; OR 3.6; 95% CI, 2.1-6.1) and tumor type (BC vs. other tumors; OR, 2.5; 95% CI, 1.2-5.0). Additional results will be presented, including for the non BC patients.
Conclusions
In this population, higher incidence of ILD related to T-DXd treatment was observed among pts from Japan and those with BC. However, these results should be interpreted with caution given that the majority of patients in the analysis had BC.
Clinical trial identification
NCT02564900, protocol submitted September 2015 - NCT03248492, protocol submitted August 2017.
Editorial acknowledgement
Medical writing support was provided by RTI Health Solutions and funded by DSI.
Legal entity responsible for the study
Medical writing support was provided by RTI-HS and funded by DSI.
Funding
Daiichi Sankyo, Inc (DSI). DSI contracted with RTI Health Solutions (RTI-HS) to complete specific tasks. DSI and AstraZeneca are collaborators on this project.
Disclosure
C.A. Powell: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Siemens; Advisory/Consultancy: Ethicon; Advisory/Consultancy: Voluntis; Research grant/Funding (institution): NIH. D.R. Camidge: Advisory/Consultancy, 2020 SAB: Anchiarno; Advisory/Consultancy, 2020 Consultation: Amgen; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), 2017-2020: Company and investigator initiated trials; Consultations: Takeda; Advisory/Consultancy, 2020 Consultation: Roche; Advisory/Consultancy, 2019-2020 Consultation: EMD Serono; Advisory/Consultancy, 2020 Consultation: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), 2020 Consultation; 2018-2020: Company sponsored trials at institution (PI role): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role); 2019 Consultation: AbbVie; Advisory/Consultancy, Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role); 2018 Consultation: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), 2018-2019: Consultation; 2018-2020: Company sponsored trials at institution (PI role): BMS; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): GSK; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Hansoh; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Inhibrx; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Lycera; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Medimmune; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Merck; Advisory/Consultancy, 2019 DSMB: Bio-Thera; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Phosplatin; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Psioxus; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Rain; Advisory/Consultancy, Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role); 2018 Consultation: Roche/Genentech; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Seattle Genetics; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institutions (PI role): Symphogen; Research grant/Funding (institution), 2018-2020: Company sponsored trials at institution (PI role): Tolero; Advisory/Consultancy, 2019 Consultation: CBT Pharmaceuticals; Advisory/Consultancy, 2018-2019 ILD adjudication committee: Daiichi-Sankyo; Advisory/Consultancy, 2018-2019 DSMB: G1 Therapeutics; Advisory/Consultancy, 2018-2019 Consultation: Blueprint; Advisory/Consultancy, 2019 Consultation: Achilles; Advisory/Consultancy, 2019 Consultation: BeyondSpring; Advisory/Consultancy, standing SRC: Apollomics; Advisory/Consultancy, standing SRC: 14ner/Elevation ; Advisory/Consultancy, 2019 Consultation: Archer; Advisory/Consultancy, 2019 Consultation: Helssin; Advisory/Consultancy, 2019 Consultation: Eli Lilly; Advisory/Consultancy, 2019 Consultation: Medtronic; Advisory/Consultancy, 2018-2019 Consultation: Ribon; Advisory/Consultancy, 2018 Consultation: Arrys/Kyn; Advisory/Consultancy, 2018 Consultation: Regeneron; Advisory/Consultancy, 2018 Consultation: Hengrui; Advisory/Consultancy, 2018 SRC: Hansoh; Advisory/Consultancy, 2018 Consultation: Inivata. S. Modi: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Macrogenics; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Research grant/Funding (institution): Novartis. A. Qin: Full/Part-time employment: Daiichi Sankyo. C. Taitt: Full/Part-time employment: Daiichi Sankyo. C. Lee: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. M.D. Hackshaw: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. J. Singh: Full/Part-time employment: Daiichi Sankyo. H. Iwata: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): MSD; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Nihonkayaku; Research grant/Funding (institution): Bayer.