H. Iwata (Nagoya, Ai, Japan)
Aichi Cancer Center HospitalAuthor Of 2 Presentations
Invited Discussant LBA4, 95MO and 4MO_PR (ID 269)
92O - Analysis of study drug-related interstitial lung disease (ILD) in patients (pts) with HER2+ metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T-DXd) (ID 252)
Abstract
Background
The phase (ph) II DESTINY-Breast01 trial showed strong efficacy of T-DXd (objective response rate, 61.4%; median progression-free survival, 19.4 mo) and manageable safety in pts with pretreated HER2+ mBC (Modi SABCS 2020), supporting approval for treatment (tx) of pts with HER2+ mBC that has progressed on ≥2 anti-HER2 therapies (US/EU) or after chemotherapy (Japan). ILD is an important identified risk with T-DXd. We characterized ILD in pts with HER2+ mBC treated with T-DXd across ph 1 and 2 trials.
Methods
Pts with HER2+ mBC who received the approved dose of T-DXd monotherapy (5.4 mg/kg every 3 wk) in 2 ph 1 studies (J101 [NCT02564900], A104 [NCT03383692]) and the ph 2 DESTINY-Breast01 (NCT03248492) trial between Aug 2015 and June 08, 2020 (data cutoff) were included. Imaging and clinical data (baseline through time of potential ILD case) were retrospectively reviewed by an independent adjudication committee. We report ILD events adjudicated as drug related.
Results
245 pts with heavily pretreated HER2+ mBC were included (ph 1, 61; ph 2, 184). Median T-DXd tx duration was 9.7 mo (range, 0.7-40.3 mo). 38 pts (15.5%) experienced an event adjudicated as drug related ILD; most were grade (G) 1/2 (30 [12.2%]). One pt each had G3 and G4 events (0.4%) and 6 had G5 ILD (2.4%). Median time to first ILD event was 5.6 mo (range, 1.1-20.8 mo) with 37/38 pts (97%) having first onset before 12 mo. 42% of pts were treated >12 mo and risk of new ILD (any grade) beyond 12 mo was low (conditional probability, 1.8%). For 27/44 events (61%), the adjudication committee assessed onset of ILD as being earlier than that reported by investigators (median difference, 52 d; range, 1-288 d). Data on use of steroids to manage ILD will be presented.
Conclusions
At the approved dose of T-DXd, most ILD events were low grade and occurred in the first 12 mo with an apparent decreased risk after 12 mo of tx; additional follow-up is needed to confirm. The adjudication committee assessed onset of ILD as being earlier than the investigators in the majority of cases, highlighting the need for close monitoring to allow for earlier identification and effective management of ILD using updated guidelines.
Clinical trial identification
NCT02564900, NCT03383692, NCT03248492.
Editorial acknowledgement
Medical editorial assistance was provided by Michael Demars, PhD (ArticulateScience LLC), and funded by AstraZeneca Pharmaceuticals LP.
Legal entity responsible for the study
Daiichi Sankyo, Inc. and Daiichi Sankyo Co., Ltd.
Funding
AstraZeneca Pharmaceuticals LP. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan.
Disclosure
C.A. Powell: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Voluntis. S. Modi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research support: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research support: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research support: AstraZeneca; Advisory/Consultancy: Macrogenics; Speaker Bureau/Expert testimony, Research grant/Funding (self), Research support: Seattle Genetics; Research grant/Funding (self), Research support: Novartis. H. Iwata: Non-remunerated activity/ies, Support of parent study and funding of editorial support: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; 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. S. Takahashi: Research grant/Funding (self), Grant, personal fees: Daiichi Sankyo; Research grant/Funding (self), Grant, personal fees: Eisai; Research grant/Funding (self), Grant, personal fees: Novartis; Research grant/Funding (self), Grant, personal fees: Taiho; Research grant/Funding (self), Grant, personal fees: MSD; Research grant/Funding (self), Grant, personal fees: Chugai; Research grant/Funding (self), Grant, personal fees: Bayer; Research grant/Funding (self), Grant, personal fees: AstraZeneca. K. Nie: Full/Part-time employment: AstraZeneca. A. Qin: Full/Part-time employment: Daiichi Sankyo. J. Singh: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. C. Taitt: Full/Part-time employment: Daiichi Sankyo; Shareholder/Stockholder/Stock options, Full/Part-time employment, employment & stock ownership in past 2 years: BMS. S. Verma: Advisory/Consultancy: Amgen; Advisory/Consultancy, Full/Part-time employment: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Lilly; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Spectrum Pharmaceuticals; Full/Part-time employment: AstraZeneca. D.R. Camidge: Honoraria (self): Daiichi Sankyo.