Abstract 190P
Background
Safety and effectiveness of T-DXd should be characterized in real world (RW) settings. We designed an observational study to address RW evidence gaps and highlight the first clinical experiences with T-DXd for HER2+ m/u BC pts.
Methods
REALITY-01 is an ambispective phase IV study that includes HER2+ m/u BC pts who received T-DXd after ≥ 2 prior lines of anti-HER2+ treatments (tt) through an early access program or after marketing authorization. Interim analysis on safety and effectiveness data are presented.
Results
At data cut-off, 305 pts were enrolled in 56 centers (median follow-up of 17.7 months (mo)). At the start of T-DXd, median age was 59 years (17.7% pts were ≥ 70 years) and 22.1% (n=60) of pts had CNS metastasis (mCNS) including leptomeningeal disease. 69% (n=187) and 15.5% (n=42) of pts had ECOG 0-1 and ECOG 2-3. 51, 7% of pts received ≥4 lines before T-DXd. Median duration of T-DXd tt was 12.5 mo. Incidence and severity of T-DXd-related adverse drug reactions (ADR) of interest in general and a focus on interstitial lung disease (ILD) are presented in the table. Median progression free survival (mPFS) was 17.4 mo [95%CI: 15.6;19.6] and objective response rate was 49.7% [95%CI: 42.3;57.2], including 24.9% (n=46) of complete response (CR). For the study population, median overall survival (OS) was not reached. For pts with mCNS at inclusion, CNS response rate was 52.4% [36.4;68.0], including 19% (n=8) of CR. Table: 190P
Primary endpoint: Percentage of pts with at least one T-DXd related ADR of interest during the 2 years following the start of T-DXd administration
| Total n=305 | ||
| Total number of pts with any ADR n(%) [95%CI] | 240 (78.7) [73.7;83.1] | |
| Leading to T-DXd | Dose reduction | 44 (14.4) |
| Discontinuation | 31 (10.2) | |
| Interruption | 66 (21.6) | |
| Any serious | 29 (9.5) | |
| Grades (worst grade) | ||
| 1 | 69 (22.6) | |
| 2 | 66 (21.6) | |
| 3 | 96 (31.5) | |
| 4 | 4 (1.3) | |
| 5 | 3 (1.0) | |
| Any ILD – no. (%) | 43 (14.1) | |
| 1 | 14 (4.6) | |
| 2 | 16 (5.2) | |
| 3 | 7 (2.3) | |
| 4 | 0 | |
| 5 | 3 (1.0) |
Conclusions
These first results from REALITY-01 confirm the safety and effectiveness of T-DXd in heavily pre-treated HER2+ m/u BC pts with or without mCNS and are consistent with DESTINY-Breast01/02 results.
Clinical trial identification
NCT05149014.
Legal entity responsible for the study
Daiichi Sankyo France.
Funding
Daiichi Sankyo France, AstraZeneca France.
Disclosure
J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, Exact Sciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. B. Asselain: Financial Interests, Personal, Advisory Role: Daiichi Sankyo France, BMS, Gilead, Roche, AstraZeneca, Servier. L. Teixeira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen. C. Levy: Non-Financial Interests, Institutional, Invited Speaker: Gilead, Pfizer; Financial Interests, Personal, Sponsor/Funding: Lilly; Non-Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Novartis, Roche. N. Hajjaji: Financial Interests, Personal, Advisory Board: Daiichi, AstraZeneca, Lilly, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: Pfizer. L. Uwer: Financial Interests, Personal, Other: Pfizer, Lilly, Amgen, Seagen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca. E. Legouffe: Financial Interests, Personal, Other: Pfizer, Novartis, Lilly, MSD, AstraZeneca, Daiichi Sankyo, Seagen, GSK, Gilead. B. Verret: Non-Financial Interests, Institutional, Advisory Role: Lilly, Daiichi Sankyo, Novartis, MSD, AstraZeneca, Owkins; Financial Interests, Personal, Advisory Role: Pfizer, Netcancer, Pierre Fabre, Seagen, Gilead. A. Moreira: Financial Interests, Personal, Advisory Board: Daiichi Sankyo France, AstraZeneca, Novartis, MSD; Financial Interests, Personal, Other, Travel, congress: Gilead; Financial Interests, Personal, Invited Speaker, Travel, congress: Daiichi Sankyo; Financial Interests, Personal, Principal Investigator: MSD. J. Grenier: Financial Interests, Personal, Advisory Role: Daiichi Sankyo France, Gilead; Financial Interests, Personal, Other, Travel, accomodations, expenses: Lilly. C. Jouannaud: Financial Interests, Personal, Other, Honoraria: Pfizer, Daiichi Sankyo, Gilead Sciences; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: MSD Oncology, Viatris. R. Nguefack: Financial Interests, Personal, Other, Congress: Lilly, Pfizer, Novartis, Gilead. C. Costan: Financial Interests, Personal, Advisory Role, Occasional: MSD, Daiichi Sankyo, Pfizer, Seagen. M.D. Saghatchian: Financial Interests, Personal, Advisory Role: AstraZeneca, Gilead, MSD, Pfizer, Lilly, Viatris, Menarini-Stemline; Non-Financial Interests, Institutional, Advisory Role: Daiichi Sankyo, Novartis. S. Kotti: Other, Personal, Project Lead, Full employment: Daiichi Sankyo France. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. All other authors have declared no conflicts of interest.