Novel Antibody-Drug-Conjugates in Routine Clinical Practice for the Treatment of Metastatic Breast Cancer: Adherence, Efficacy and Tolerability – Real-World Data from German Breast Centers

Abstract

Introduction

The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts.

Materials and Methods

This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers.

Results

125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4–11.6) and 11.8 months for SG (95% CI: 8.0–14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8–12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8–6.3) with SG (TNBC 4.9; HR+/HER2−: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1–not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7–not estimable) with SG therapy (TNBC: 12.4, HR+/HER2−: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG.

Conclusion

Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.

Zusammenfassung

Einleitung

Trastuzumab-Deruxtecan (T-DXd) und Sacituzumab-Govitecan (SG) sind Antikörper-Wirkstoff-Konjugate (ADCs) der 3. Generation, die vor Kurzem zur Behandlung von metastatischem Brustkrebs über mehrere Subtypen hinweg und in verschiedenen therapeutischen Zusammenhängen zugelassen wurden.

Material und Methoden

Ziel dieser retrospektiven multizentrischen Studie war es, die Real-World-Daten über die Verträglichkeit, Umsetzbarkeit und Wirksamkeit dieser Wirkstoffe in einer vorbehandelten Real-World-Kohorte in 3 großen deutschen Brustkrebszentren zu bewerten.

Ergebnisse

Eingeschlossen wurden 125 Patientinnen, die zwischen November 2020 und Juni 2023 mit T-DXd oder SG behandelt wurden (T-DXd: 77 Patientinnen; SG: 48 Patientinnen). Die mediane Behandlungsdauer betrug 6,0 Monate für eine T-DXd- und 3,5 Monate für eine SG-Therapie mit einer medianen Nachbeobachtungszeit von 10,4 Monaten für T-DXd (95%-KI: 8,4–11,6) und 11,8 Monaten für SG (95%-KI: 8,0–14,4). 33,3% der Patientinnen entwickelten eine schwere Neutropenie (CTC ≥ III°) im Verlauf der SG-Therapie, wobei eine numerische Reduktion nach dem primären prophylaktischen Einsatz von G-CSF beobachtet wurde. Bei 8 von 77 Patientinnen (10,4 %) trat eine T-DXd-bedingte Pneumonitis auf. Das mediane progressionsfreie Überleben (mPFÜ) betrug 8,6 Monate (95%-KI: 5,8–12,4) mit T-DXd (HER2+: 10,8; HER2-low: 4,7) und 4,9 Monate (95%-KI: 2,8–6,3) mit SG (TNBC 4,9; HR+/HER2−: nicht erreicht). Das mediane Gesamtüberleben (GÜ) betrug 23,8 Monate (95%-KI: 16,1–nicht schätzbar) mit einer T-DXd-Therapie (HER2+: 27,1; HER2-low: nicht erreicht) und 12,4 Monate (95%-KI: 8,7–nicht schätzbar) mit einer SG-Therapie (TNBC: 12,4, HR+/HER2−: nicht erreicht). Verabreicht wurden 95,7% der im Protokoll vorgegebenen therapeutischen T-DXd-Dosis bzw. 89,6% der vorgegebenen SG-Dosis.

Schlussfolgerung

Insgesamt weisen die Daten auf eine gute Umsetzbarkeit, Wirksamkeit und Verträglichkeit von ADC-Therapien in einer realen Umgebung hin.

Keywords

oncology - breast cancer - systemic therapy - ADCs - sacituzumab govitecan - trastuzumab deruxtecan - real-world evidence

Schlüsselwörter

Onkologie - Brustkrebs - systemische Therapie - ADCs - Sacituzumab-Govitecan - Trastuzumab-Deruxtecan - Real-World Evidence

Publication History

Received: 11 May 2024

Accepted after revision: 28 July 2024

Article published online:
02 September 2024

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