臨床研究等提出・公開システム

A multicenter cohort study on post-trastuzumab deruxtecan treatment in patients with breast cancer in the 'Post-marketing Surveilance for interstitial lung disease of ENHERTU in breast cancer patients' (EN-SEMBLE)

EN-SEMBLE

664

Patients with HER2 positive metastatic/recurrent breast cancer who started treatment for T-DXd between May 25, 2020, and November 30, 2021, and were enrolled in all-case surveys and who met all inclusion and did not meet exclusion criteria were included. The mean (minimum-maximum) age at the start of the 1st post-treatment was 60.0 (30-89) years, with 37.3% (248/664) aged >=65 years and 62.7% (416/664) aged <65 years. The gender was 0.5% (3/664) in males and 99.5% (661/664) in females. The pharmacotherapies selected in the 1st post-treatment were Anti-HER2 therapy in 73.3% (487/664 cases), Molecular targeted therapy (other than Anti-HER2 therapy) in 11.7% (78/664 cases), Immune checkpoint inhibitor in 0.3% (2/664 cases), Chemotherapy in 73.2% (486/664 cases), Endocrine therapy in 15.2% (101/664 cases), and Others in 1.5% (10/664 cases).

Enrollment began on December 12, 2022, and enrollment was completed on June 23, 2023. In addition, the breakdown of the analysis population was as follows: There were 1213 patients who received T-DXd between May 25, 2020, and November 30, 2021 (3 of whom were started after December 1, 2021), and 538 patients were excluded, resulting in 675 patients enrolled. In addition, 11 of the enrolled study subjects were excluded from the analysis, so the number of patients included in the analysis was 664.

Not applicable

Distributions of pharmacotherapy (post-treatment) for HER2 positive metastatic/recurrent breast cancer performed after discontinuation of T-DXd 1) Selected pharmacotherapy in the post-treatment (The 1st post-treatment, The 2nd post-treatment) The 1st post-treatment was Anti-HER2 therapy in 73.3% (487/664 cases), Molecular targeted therapy (other than Anti-HER2 therapy) in 11.7% (78/664 cases), Immune checkpoint inhibitor in 0.3% (2/664 cases), Chemotherapy in 73.2% (486/664 cases), Endocrine therapy in 15.2% (101/664 cases), and Others in 1.5% (10/664 cases). The 2nd post-treatment was Anti-HER2 therapy in 67.2% (275/409 cases), Molecular targeted therapy (other than Anti-HER2 therapy) in 12.0% (49/409 cases), Immune checkpoint inhibitor in 1.0% (4/409 cases), Chemotherapy in 76.3% (312/409 cases), Endocrine therapy in 12.0% (49/409 cases), and Others in 1.0% (4/409 cases). 2) Distribution of the 1st post-treatment regimen The regimens of pharmacotherapy administered in the 1st post-treatment were as follows: Anti-HER2 therapy plus Chemotherapy in 54.1% (359/664 cases), Anti-HER2 therapy in 10.8% (72/664 cases), Chemotherapy in 9.6% (64/664 cases), Molecular targeted therapy (other than Anti-HER2 therapy ) plus Chemotherapy in 8.0% (53/664 cases), Anti-HER2 therapy plus Endocrine therapy in 6.8% (45/664 cases), Endocrine therapy in 4.2% (28/664 cases), Molecular targeted therapy (other than Anti-HER2 therapy ) plus Endocrine therapy in 3.0% (20/664 cases), and other regimens in 1% or less. 3) PFS of the 1st post-treatment The median PFS of the 1st post-treatment in all (664) patients included in the analysis was 4.14 months (95% confidence interval, 3.88 months-4.53 months). The event-rate was 79.8% (530/664 cases), including 76.5% (508/664 cases) of PD and 3.3% (22/664 cases) of deaths during the 1st post-treatment. Censoring was 20.2% (134/664 patients). The rates of PFS at every time point from the date of initiation of 1st post-treatment were 36.1% (95% confidence interval, 32.3%-39.9%) at 6 months, 18.9% (95% confidence interval, 15.8%-22.3%) at 12 months, 11.3% (95% confidence interval, 8.6%-14.3%) at 18 months, and 8.8% (95% confidence interval, 6.3%-11.8%) at 24 months. After T-DXd therapy The median PFS by regimen was 4.14 months (95% confidence interval, 3.71 months to 4.96 months) for trastuzumab plus pertuzumab regimen, 4.37 months (95% confidence interval, 3.48 months to 5.06 months) for trastuzumab regimen ,2.56 months (95% confidence interval, 0.95 months to 3.06 months) for Anti-HER2 therapy(T-DM1/others) , 5.55 months (95% confidence interval, 1.91 months to 6.93 months) for ET, and 4.14 months (95% confidence interval ,2.79 months to 5.39 months) for Molecular targeted therapy (other than CDK4/6), 6.67 months (95% confidence interval, 2.50 months-10.84 months) for CDK4/6, 2.79 months (95% confidence interval, 2.07 months-3.94 months) for other CTx, 4.21 months (95% confidence interval, 3.71 months to 5.78 months) for Lapatinib, 8.97 months (95% confidence interval, 2.10 months)for Other HER2-TKIs, and 3.07 months (95% confidence interval, 0.07 months-9.46 months)for Others. 4) TTF after T-DXd therapy The median TTF after T-DXd therapy in all (664) patients included in the analysis was 3.84 months (95% confidence interval, 3.68 months-4.14 months). The event rate was 89.9% (597/664 patients), including treatment discontinuation in 89.8% (596/664 patients) and death in 0.2% (1/664 patients). Censoring was 10.1% (67/664 patients). The percentages of TTF at every time point from the date of initiation of the 1st post-treatment were 33.1% (95% confidence interval, 29.5%-36.7%) at 6 months, 16.0% (95% confidence interval, 13.3%-18.9%) at 12 months, 8.6% (95% confidence interval, 6.5%-11.1%) at 18 months, and 7.0% (95% confidence interval, 5.0%-9.4%) at 24 months. After T-DXd therapy The median TTF was 3.94 months (95% confidence interval, 3.48 months to 4.40 months) for trastuzumab plus pertuzumab regimen, 3.84 months (95% confidence interval, 3.25 months to 4.60 months)for trastuzumab regimen, 1.87 months (95% confidence interval, 0.69 months to 3.02 months)for Anti-HER2 therapy(T-DMI/others), 3.84 months (95% confidence interval, 1.41 months to 6.70 months)for ET, 3.71 months (95% confidence interval, 2.76 months-4.80 months) for Molecular targeted therapy(other than CDK4/6), 6.41 months (95% confidence interval, 2.50 months-7.39 months)for CDK4/6, 2.45 months (95% confidence interval, 2.07 months-3.78 months) for Other CTx,4.17 months (95% confidence interval, 3.71 months-5.55 months) for Lapatinib, 8.23 months (95% confidence interval, 2.10 months-) for Other HER2-TKIs, and 3.07 months (95% confidence interval, 0.82 months to 9.46 months) for Others.

This study enrolled 664 patients, and approximately 70% chose anti-HER2 therapy as drug therapy after discontinuing T-DXd. Median PFS for the overall population was 4.14 months (95% confidence interval, 3.88 months-4.53 months).

April. 01, 2025

Yes

The datasets obtained and analyzed in this study will be disclosed by the principal investigator upon legitimate request.

https://jrct.mhlw.go.jp/latest-detail/jRCT1030220506

Tsurutani Junji

Showa University Hospital

1-5-8 Hatanodai Shinagawa-ku Tokyo

tsurutaj@med.showa-u.ac.jp

Shibata Reiko

EPS Corporation

Maruito Daini Esaka Bldg. 1-17-6 Esakacho Suita-shi

+81-671765731

prj-enh-ds-21008_b@eps.co.jp

Complete

Dec. 01, 2022

Observational

1)Patients who received T-DXd for HER2-positive unresectable and/or recurrent breast cancer between May 25, 2020 and November 30, 2021.
2)Patients enrolled in the "Post-marketing Surveillance for interstitial lung disease of ENHERTU in breast cancer patients"
3)Patients who started post-treatment after discontinuation of T-DXd
4)Patients who are 18 years of age or older at the start of post-treatment.
5)Patients who have given written informed consent (however, patients who cannot give written informed consent due to death or loss of follow-up will be allowed to opt out).

1)Patients who are deemed inappropriate by the investigator.

Both

HER2-positive unresectable and/or recurrent breast cancer

1.Distribution of post-treatment regimen
2.Effectiveness and safety endpoints in all subjects and by post-treatment regimen
-Progression Free Survival (PFS)
-Time to Treatment Failure (TTF)
-Time to Next Treatment (TTNT)
-Overall Survival (OS)
-Objective response rate (ORR)
-PFS2
-TTF2
-Incidence rate of Interstitial lung disease (ILD)
3.Exploratory endpoint
-PFS2 that the starting point is regarded as the first dose date of T-DXd treatment
-TTF2 that the starting point is regarded as the first dose date of T-DXd treatment
4.Distribution and effectiveness and safety of post-treatment regimens in subgroups

+81-3-3784-8129

Oct. 26, 2022

none