431P - Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the TROPION-Breast01 study of datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of chemotherapy (ICC) in patients (pts) with pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC)

Background

In TROPION-Breast01 (TB-01; NCT05104866), the antibody-drug conjugate Dato-DXd showed improved efficacy vs ICC in pts with HR+/HER2– BC [Bardia et al. ESMO 2023]. The Dato-DXd safety profile was manageable. The most common treatment (Tx)-related AEs (TRAEs) were nausea and stomatitis; ICC was notable for high rates of grade 3/4 neutropenia. Here we report an analysis of EAIRs of AEs in the context of the longer Tx duration with Dato-DXd vs ICC (median 6.7 vs 4.1 mo).

Methods

The TB-01 study design was previously described. EAIRs were derived from a post-hoc analysis and were expressed as subject rate (per 100 pt yrs) and calculated as number of pts with AEs divided by the total duration of Tx across all pts per group (see Table) x 100.

Results

Absolute incidence rates of TRAEs with Dato-DXd were 93.6% and 86.3% with ICC; Dato-DXd had less than half the proportion of G≥3 TRAEs vs ICC. Other absolute incidence rates with Dato-DXd, including Tx-related serious AEs (TRSAEs) and TRAEs leading to Tx discontinuation, were lower than or similar to ICC. However, EAIRs were lower for Dato-DXd vs ICC across all such summary AE categories, illustrating that the longer Dato-DXd Tx duration did not impact AE incidence rates per 100 pt yrs (Table). For the most frequent TEAEs with absolute incidence ≥5% in both arms, EAIRs ≥2x higher with ICC vs Dato-DXd were neutropenia (63 vs 9; ratio 6.9:1), decreased neutrophil count (55 vs 12; 4.7:1), diarrhea (47 vs 19; 2.4:1), anemia (61 vs 28; 2.2:1) and headache (27 vs 13; 2.1:1). In the Dato-DXd arm, only stomatitis was ≥2x higher vs ICC (93 vs 36; 2.6:1). Table: 431P

Safety summary of absolute incidence and EAIRs – All Investigator-assessed*

Data cutoff 17 July 2023. *EAIRs expressed as subject rate (per 100 pt yrs).

Conclusions

After adjusting for Tx duration, Dato-DXd is more tolerable vs ICC across all AE categories and for a majority of individual AEs, further emphasising the potential for Dato-DXd as a well tolerated Tx option.

Clinical trial identification

NCT05104866, Release date: 3 Nov 2021.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Catherine Crookes 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

H.S. Rugo: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Napo Pharmaceuticals, Puma Biotechnology, Mylan, 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. A. Bardia: Financial Interests, Personal, Advisory Role, Consulting or 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 or 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 or 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, accommodation, expenses: Gilead Sciences, AstraZeneca, Roche, Pfizer; Financial Interests, Institutional, Funding, Research funding (to institution): Roche. M. De Laurentiis: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Exact Science, Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Institutional, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai. S. Wang: Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding: AstraZeneca. N. Martinez: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Novartis, Lilly, Pfizer, Roche, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai; Financial Interests, Institutional, Principal Investigator: Novartis, Eli Lilly, Pfizer, Roche, Sanofi, MSD, Seagen, Gilead, Daiichi Sankyo, AstraZeneca, Eisai. G. Santos Borges: Non-Financial Interests, Personal, Principal Investigator: TROPION-Breast01 (uncompensated). D. Cescon: Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, GSK, Inflex, Inivata/NeoGenomics, Lilly, Merck, Novartis, Pfizer, Roche, Saga; Financial Interests, Institutional, Funding, Research funding to institution: AstraZeneca, Guardant Health, Gilead, GSK, Inivata/NeoGenomics, Knight, Merck, Pfizer, ProteinQure, Roche; Financial Interests, Personal, Royalties, 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, Advisory Role, Honoraria: Chugai Pharma, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD K.K. Y. Lu: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Pfizer, Roche, Novartis, Lilly; Financial Interests, Personal, Other, Travel, accommodation, expenses: Novartis; Financial Interests, Personal, Advisory Role, Honoraria: Pfizer, Roche, MSD, Novartis, Lilly, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, EuroPharma; Financial Interests, Institutional, Funding, Research funding (to institution): Novartis, MSD, AstraZeneca. J. Tsurutani: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Daiichi Sankyo, Lilly, AstraZeneca, Seagen; Financial Interests, Personal, Advisory Role, 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). S.M. Tolaney: Financial Interests, Personal, Advisory Role, Consulting or advisory Role: Novartis, Pfizer (Seagen), Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Umoja Biopharma, ; Financial Interests, Institutional, Funding, Research Funding (to institution): Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Gilead, Seattle Genetics, OncoPep, Daiichi Sankyo; Financial Interests, Personal, Other, Travel: Eli Lilly, Sanofi, Gilead, Jazz Pharmaceuticals. D. Mapiye: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. K. Atuah; D. Verma; S. Khan: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. B. Xu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca, Novartis. B. Pistilli: Financial Interests, Institutional, Advisory Role, Consulting fees (institutional): AstraZeneca, Seagen, Gilead, Novartis, Lilly, MSD, Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting fees (personal): 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. K. Jhaveri: Financial Interests, Personal, Advisory Role, Consulting or 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, accommodation, expenses: 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.