LBA2 - Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC): Additional safety analysis from TROPION-Breast01

Background

In TROPION-Breast01 (NCT05104866), the antibody-drug conjugate Dato-DXd showed improved efficacy and was well tolerated compared with investigator’s choice of CT (ICC) in patients (pts) with HR+/HER2– BC. Here we report additional safety analyses.

Methods

Study design was previously described; safety was a secondary endpoint. Mouthwash use was advised (steroid mouthwash strongly recommended if available), and ophthalmologic assessment was required per regulatory request at screening and every three 21-day cycles.

Results

At data cutoff (Jul 2023), 360 pts received Dato-DXd, 351 ICC. Median treatment duration was longer with Dato-DXd vs ICC (6.7 vs 4.1 mo). Rate of ≥G3 treatment-related adverse events (TRAEs) was lower with Dato-DXd vs ICC (21% vs 45%). TRAEs of special interest (AESIs) with Dato-DXd included stomatitis/oral mucositis (OM) (56%), ocular events (OE; 40%), and adjudicated drug-related interstitial lung disease (ILD; 3%). OE were identified mainly via mandatory eye exams; >50% were dry eye. Stomatitis/OM and OE were mostly low grade (asymptomatic/mild, G1 in 25% and 32% of all Dato-DXd pts, respectively); both were well managed by toxicity management guidelines (TMGs), with low rates of dose interruption (1% and 3%) and discontinuation (both 0.3%). In contrast, the ICC safety profile was most notable for high-grade neutropenia (≥G3 in 31% of ICC pts) leading to dose interruption (17%)/reduction (13%). Adjudicated drug-related ILD with Dato-DXd was mostly low grade (asymptomatic, G1 in 1% of Dato-DXd pts). AESIs generally occurred in the first few cycles: median onset of stomatitis/OM at Cycle 2, OE at Cycle 3, ILD at Cycle 4. Median time to resolution was 37, 67, 28 days for stomatitis/OM, OE, ILD.

Conclusions

Further data from TROPION-Breast01 showed that AESIs with Dato-DXd were typically low grade, occurred in the first few cycles and were manageable using TMGs. Moreover, with Dato-DXd the rate of ≥G3 TRAEs was less than half that with ICC and fewer TRAEs led to dose interruption/reduction, showing that Dato-DXd offers better tolerability vs ICC and further emphasizing the potential for Dato-DXd as a favourable treatment option in clinical practice.

Clinical trial identification

NCT05104866.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Funding

AstraZeneca PLC in collaboration with Daiichi Sankyo.

Disclosure

K. Jhaveri: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Pfizer, AstraZeneca, Jounce Therapeutics, Synthon, Intellisphere, BMS, Genentech, AbbVie, Lilly, BluePrint Medicines, Seagen, Daiichi Sankyo, Biotheranostics, Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead Sciences, Scorpio; Financial Interests, Personal, Other, Travel support: Taiho Pharmaceutical, Jounce Therapeutics, Pfizer, AstraZeneca, Intellisphere, Lilly, Gilead Sciences, Genentech/Roche; Financial Interests, Institutional, Funding, Research funding (to institution): Novartis, Genentech, Debiopharm Group, ADC Therapeutics, Pfizer, Novita Pharmaceuticals, Clovis Oncology, Lilly, Zymeworks, Immunomedics, Puma Biotechnology, VelosBio/Merck, AstraZeneca, Context Therapeutics, Scorpion Therapeutics, Blueprint Medicines. A. Bardia: Financial Interests, Personal, Advisory Role, Consulting/Advisory role (personal): Novartis, Genentech, Pfizer, Merck, Sanofi, Daiichi Sankyo, AstraZeneca, Lilly, Gilead Sciences, Menarini, Mersana; Financial Interests, Institutional, Advisory Role, Consulting or advisory role (to institution): Novartis, Genetech/Roche, Pfizer, Radius Health, Innocrin Pharma, Lilly, Gilead Sciences, Menarini; Financial Interests, Institutional, Funding, Research funding (to institution): Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, AstraZeneca, Daiichi Sankyo. S. Im: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: AstraZeneca, Novartis, Roche/Genentech, Eisai, Pfizer, Amgen, Hanmi, Lilly, MSD, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding (to institution): AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical, Eisai, Boryung Pharmaceuticals. S. Pernas Simon: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Seagen, Pfizer, Pierre Fabre, Daiichi Sankyo/AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly, Roche, Gilead Sciences, Pfizer, Daiichi Sankyo/AstraZeneca; Financial Interests, Personal, Other, Travel support: Gilead Sciences, AstraZeneca, Roche, Pfizer; Financial Interests, Institutional, Funding, Research funding (to institution): Roche. M. De Laurentiis: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Exact Science, Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Personal, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai. S. Wang: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, AstraZeneca, Novartis, Lilly; Financial Interests, Institutional, Funding, Research funding: Pfizer, AstraZeneca. N. Martinez: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Lilly, Pfizer, Roche, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Personal, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai. G. Santos Borges: Non-Financial Interests, Personal, Principal Investigator, Uncompensated: TROPION-Breast01. D.W. Cescon: Financial Interests, Institutional, Advisory Role, Consulting/Advisory role: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Inflex, Inivata/NeoGenomics, Lilly, Merck, Novartis, Pfizer, Roche, Saga; Financial Interests, Institutional, Funding, AstraZeneca, Guardant Health, Gilead, GSK, Inivata/NeoGenomics, Knight, Merck, Pfizer, ProteinQure and Roche: AstraZeneca, Guardant Health, Gilead, GSK, Inivata/NeoGenomics, Knight, Merck, Pfizer, ProteinQure, Roche; Financial Interests, Personal, Royalties, Patent: US62/675,228, for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene: Patent: US62/675,228. M. Hattori: Financial Interests, Personal, Invited Speaker, Honoraria: Chugai Pharma, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD K.K. Y. Lu: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Pfizer, Roche, Novartis, Lilly; Financial Interests, Personal, Other, Travel/Accommodation expenses: Novartis; Financial Interests, Personal, Invited Speaker, Honoraria: Pfizer, Roche, MSD, Novartis, Lilly, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, EuroPharma; Financial Interests, Institutional, Funding, Research funding (to institution): Novartis, MSD, AstraZeneca. E.P. Hamilton: Financial Interests, Institutional, Funding, Research funding (to institution): AstraZeneca, Hutchinson MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millennium, TapImmune, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health; Financial Interests, Institutional, Advisory Role, Consulting fees (to institution): Pfizer, Genentech/Roche, Lilly, Puma Biotechnology, Daiichi Sankyo, Mersana, Boehringer Ingelheim, AstraZeneca, Novartis, Silverback Therapeutics, Black Diamond, CytomX Therapeutics, Dantari, H3 Biomedicine, Merck, SeaGen, Eisai, Deciphera, Arvinas, Arcus. J. Tsurutani: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Daiichi Sankyo, Lilly, AstraZeneca, Seagen; Financial Interests, Personal, Invited Speaker, Honoraria: Kyowa Kirin, Eisai, Chugai Pharma, Taiho Pharmaceutical, Nihonkayaku, Lilly Japan, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Funding, Research funding (to institution): Eisai, Boehringer Ingelheim, Lilly, MSD Oncology, Kyowa Kirin, Daiichi Sankyo, Chugai Pharma, Nihonkayaku, West Japan Oncology Group, Sant Joan de Déu Research Foundation (FSJD). K. Kalinsky: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Lilly, Novartis, AstraZeneca, Genentech/Roche, Immunomedics, Merck, Seagen, Oncosec, 4D Pharma, Daiichi Sankyo, AstraZeneca, Puma Biotechnology, Mersana, Menarini Silicon Biosystems, Myovant Sciences, Takeda, Prelude Therapeutics, RayzeBio; Financial Interests, Institutional, Funding, Research funding (to institution): Novartis, Genetech/Roche, Lilly, Seagen, AstraZeneca, Daiichi Sankyo, Ascentage Pharma; Financial Interests, Personal, Full or part-time Employment, Employment (spouse): GRAIL, EQRx; Financial Interests, Personal, Stocks/Shares, Stock ownership (spouse): GRAIL, EQRx. D. Mapiye: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Fairhurst: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M.A. Munegowda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Xu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Consulting/Advisory role: AstraZeneca, Novartis. B. Pistilli: Financial Interests, Institutional, Advisory Role, Consulting fees: AstraZeneca, Seagean, Gilead, Novartis, Lilly, MSD, Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting fees: Pierre Fabre, Daiichi Sankyo; Financial Interests, Institutional, Funding, Institutional research funding: AstraZeneca, Daiichi Sankyo, Gilead, Seagen, MSD; Financial Interests, Personal, Other, Travel support: AstraZeneca, Pierre Fabre, Lilly, Daiichi Sankyo, MSD. H.S. Rugo: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, Eisai, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding (to institution): OBI Pharma, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Astellas Pharma, Taiho Oncology, Veru, GSK, Genentech/Roche, Stemline Therapeutics.