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. 2024 Sep 2;84(9):855-865.
doi: 10.1055/a-2375-5194. eCollection 2024 Sep.

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

Henning Schäffler  1 , Dorothee Jakob  2 , Sophia Huesmann  1 , Kerstin Pfister  1 , Kristina Veselinovic  1 , Fabienne Schochter  1 , Elena Leinert  1 , Visnja Fink  1 , Brigitte Rack  1 , Alexander Englisch  3 , Lea-Louise Volmer  3 , Tobias Engler  3 , Marie Louise Frevert  2 , Ingolf Juhasz-Böss  2 , Sara Brucker  3 , Sabine Heublein  1 , Wolfgang Janni  1 , Florin-Andrei Taran  2 , Andreas Hartkopf  3 , Dominik Dannehl  3
Affiliations

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

Henning Schäffler et al. Geburtshilfe Frauenheilkd. .

Abstract
in English, German

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.

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

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Conflict of interest statement

Conflict of Interest H. Schäffler: Travel Support by Daiichi Sankyo and Gilead, Honoraria by Novartis; D. Jakob: none; S. Huesmann: none; K. Pfister: Honoraria by Pfizer Novartis and Gilead; K. Veselinovic: Honoraria by Roche, Pfizer, AstraZeneca; F. Schochter: Travel Support, Honoraria and Consulting Fees by AstraZeneca, Roche, Karyopharm, Merck, GlaxoSmithKline, Eisai, Clovis; E. Leinert: none; V. Fink: none; B. Rack: Honoraria and research funding by AstraZeneca and Novartis; A. Englisch: none; L. Volmer: none; T. Engler: Travel Support, Honoraria and Consulting Fees by AstraZeneca, GSK, Gilead, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Stemline, Roche, Daiichi Sankyo; ML. Frevert: Honoraria by Novartis; I. Juhasz-Böss: none; S. Brucker: Travel Support and Consulting Fees by Hologic, Sanofi, AstraZeneca, Lilly, MSD, Medtronic, Pfizer; S. Heublein: research funding and honoraria from Clovis Oncology, Inc., GlaxoSmithKline, Novartis, Roche, AstraZeneca and Pfizer. Participation in advisory boards for Novartis, GlaxoSmithKline, and Merck Sharp & Dohme Corporation; W. Janni: Travel Support, Honoraria and Consulting Fees by Daiichi Sankyo, AstraZeneca, Gilead; FA. Taran: Travel Support by Gilead, Consulting Fees by AstraZeneca, Gilead, MSD, ImmunoGen, Onkowissen, Roche, GSK; A. Hartkopf: Travel Support by Daiichi Sankyo, Gilead, Roche, AstraZeneca, Pfizer, Honoraria by Daiichi Sankyo, Gilead, Seagen, Roche, AstraZeneca, Pfizer, Lilly, MSD, Novartis; D. Dannehl: Travel Support by Gilead and Daiichi Sankyo, Honoraria by Gilead.

Figures

Fig. 1
Fig. 1
Real-world progression free survival and real-world overall survival with sacituzumab govitecan: The study cohort consisted of a total of 48 patients, comprising 43 patients with TNBC and 5 patients with HR+/HER2− mBC. Panel a illustrates the rwPFS of all patients treated with sacituzumab govitecan. Panel b illustrates the rwPFS for patients diagnosed with triple-negative mBC and HR+/HER2− mBC treated with sacituzumab govitecan separately. Panel c illustrates the rwOS of all patients treated with sacituzumab govitecan. Panel d illustrates the rwOS of patients diagnosed with triple-negative mBC and HR+/HER2− mBC treated with sacituzumab govitecan separately.
Fig. 2
Fig. 2
Real-world progression free survival with trastuzumab deruxtecan: The study cohort consisted of a total of 77 patients, comprising 41 patients with HER2+ mBC and 36 patients with HER2-low mBC. Panel a illustrates the rwPFS of all patients treated with T-DXd. Panel b illustrates the rwPFS for patients diagnosed with HER2+ and HER2-low mBC treated with T-DXd separately. Panel c illustrates the rwOS of all patients treated with T-DXd. Panel d illustrates the rwOS for patients diagnosed with HER2+ and HER2-low mBC treated with T-DXd separately.
See this image and copyright information in PMC

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