Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab

Abstract

The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8–7.8); in second-line treatment, 7.7 months (95% CI: 2.8–11.0); in third-line, 3.4 months (95% CI: 2.3–not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2–NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.

Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer

“…In the EMILIA study, the median PFS with T-DM1 was 9.6 months, but it must be remembered that these patients did not receive prior treatment with pertuzumab. Corresponding data from real-world registries are similar to the DESTINY-Breast03 trial, in which the median PFS was 7.7 months in second-line therapy after prior treatment with pertuzumab and 3.4 months in third-line therapy 25 . Hence, in this therapeutic setting, T-DXd significantly improved the treatment of HER2-positive breast cancer.…”

“…Therapielinie 7,7 Monate nach einer Vorbehandlung mit Pertuzumab und 3,4 Monate in der 3. Therapielinie betrug 25 . Somit konnte in dieser Therapiesituation mit T-DXd die Behandlung des HER2-positiven Mammakarzinoms deutlich verbessert werden.…”

Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer

“…In the PRAEGNANT metastatic breast cancer registry, 76 patients were treated with T-DM1 in different lines after taxane-trastuzumab-pertuzumab (39 in second-line, 25 in third-line and 12 in fourth-line or higher). This study found a median PFS with T-DM1 of 3.5 months in all patients but with a decline of PFS when T-DM1 was administered in later lines (median PFS of 7.7 months in second-line, 3.4 months in third-line and 2.7 months in fourth-line or higher) [ 12 ].…”

ErbB2/Her2-dependent downregulation of a cell death-promoting protein BLNK in breast cancer cells is required for 3D breast tumor growth

“…Approximately 15% of breast cancers overexpress ErbB2/Her2 receptor tyrosine kinase [1] and are normally treated with ErbB2targeted drugs [2,3]. Approximately 20% of such malignancies develop resistance to these agents and become incurable [2,3].…”

“…Approximately 15% of breast cancers overexpress ErbB2/Her2 receptor tyrosine kinase [1] and are normally treated with ErbB2targeted drugs [2,3]. Approximately 20% of such malignancies develop resistance to these agents and become incurable [2,3]. Conceivably, treatment efficacy of ErbB2-positive cancers could be facilitated by drugs blocking oncogenic mechanisms downstream of ErbB2.…”