Indirect Treatment Comparison between Ribociclib Combined with Non-Steroidal Aromatase Inhibitors and Ovarian Function Suppression vs. Tamoxifen in Premenopausal Women with Early Breast Cancer

Abstract

Background

This study provides an indirect treatment comparison of ribociclib combined with non-steroidal aromatase inhibitors and ovarian function suppression (ribociclib + NSAI + OFS) vs. a frequently used treatment option in German clinical routine (tamoxifen ± OFS) in premenopausal patients with HR-positive (HR+), HER2-negative (HER2−) early breast cancer (BC).

Material and Methods

Data on premenopausal women treated with ribociclib and tamoxifen were derived from the NATALEE clinical trial (NCT03701334) and the retrospective German data collection CLEAR-B, respectively. NATALEE trial eligibility criteria were applied to the CLEAR-B dataset. Standardized mortality ratio weights were used for propensity score (PS) adjustment to balance study populations. All hazard ratios (HR) were calculated based on a 4-year-observation period for both treatment arms. Effectiveness endpoints comprised invasive and distant disease-free survival (iDFS, dDFS), recurrence-free survival (RFS), and overall survival (OS). Safety-related endpoints were treatment termination (TT) and toxicity-related TT (TTtox). For safety comparisons, the ribociclib arm was divided into groups that discontinued ribociclib + NSAI + OFS or ribociclib only.

Results

Significant beneficial effects favoring ribociclib + NSAI + OFS (n = 1115) over tamoxifen ± OFS (n = 822) were observed for all effectiveness outcomes (iDFS [HR = 0.5 (95% CI 0.35; 0.71); p < 0.01]; dDFS [HR = 0.52 (95% CI 0.35; 0.77); p = 0.01], RFS [HR = 0.42 (95% CI 0.29; 0.62); p < 0.01], OS [HR = 0.34 (95% CI 0.18; 0.63); p = 0.01]) during the 4-year-observation period. The effect of early treatment discontinuation showed no significant differences between ribociclib + NSAI + OFS and tamoxifen ± OFS (TT-a: HR = 1.2 [95% CI: 0.71; 2.01], p = 0.48; TTtox-a: HR = 0.54 [95% CI 0.22; 1.30], p = 0.23).

Conclusion

In this retrospective analysis, ribociclib + NSAI + OFS demonstrated advantages across all effectiveness endpoints, including OS, in premenopausal women with HR+, HER2− early BC, without increasing overall treatment discontinuation rates compared to tamoxifen ± OFS.

Zusammenfassung

Hintergrund

Die vorliegende Studie liefert einen indirekten Behandlungsvergleich von Ribociclib kombiniert mit nichtsteroidalen Aromatasehemmern und ovarieller Funktionsunterdrückung (Ribociclib + NSAI + OFS) mit einer oft in der täglichen klinischen Praxis in Deutschland eingesetzten Behandlungsoption (Tamoxifen ± OFS) bei prämenopausalen Patientinnen mit HR-positivem (HR+), HER2-negativem (HER2−) Brustkrebs im Frühstadium (BC).

Material und Methoden

Die Daten der mit Ribociclib und Tamoxifen behandelten prämenopausalen Frauen wurden der klinischen NATALEE-Studie (NCT03701334) bzw. der retrospektiven deutschen CLEAR-B-Datensammlung entnommen. Die Einschlusskriterien der NATALEE-Studie wurden auf den CLEAR-B-Datensatz angewendet. Gewichtete standardisierte Mortalitätsverhältnisse wurden zur Adjustierung des Propensitäts-Scores (PS) eingesetzt, um die Studienpopulationen anzugleichen. Alle Hazard Ratios (HR) wurden für beide Behandlungsarme kalkuliert und bezogen sich auf einen Beobachtungszeitraum von 4 Jahren. Die Effektivitätsendpunkte waren invasives und fernes krankheitsfreies Überleben (iKFÜ, fKFÜ), rezidivfreies Überleben (RFÜ) und Gesamtüberleben (GÜ). Die sicherheitsbezogenen Endpunkte waren Beendigung der Behandlung („Treatment Termination“ [TT]) sowie toxizitätsbezogene TT (TTtox). Für den Sicherheitsvergleich wurde der Ribociclib-Arm weiter in eine Gruppe, welche die Behandlung mit Ribociclib + NSAI + OFS abbrach, und eine Gruppe, die nur Ribociclib erhielt, unterteilt.

Ergebnisse

Während des 4-jährigen Beobachtungszeitraums wurden erhebliche positive Effekte zugunsten von Ribociclib + NSAI + OFS (n = 1115) im Vergleich zu Tamoxifen ± OFS (n = 822) für alle Effektivitäts-Outcomes festgestellt (iKFÜ [HR = 0,5 (95%-KI 0,35; 0,71); p < 0,01]; fKFÜ [HR = 0,52 (95%-KI 0,35; 0,77); p = 0,01], RFÜ [HR = 0,42 (95%-KI 0,29; 0,62); p < 0,01], GÜ [HR = 0,34 (95%-KI 0,18; 0,63); p = 0,01]). Es gab keine signifikanten Unterschiede zwischen Ribociclib + NSAI + OFS und Tamoxifen ± OFS bezüglich der Auswirkungen eines frühen Behandlungsabbruchs (TT-a: HR = 1,2 [95%-KI: 0,1; 2,01], p = 0,48; TTtox-a: HR = 0,54 [95%-KI 0,22; 1,30], p = 0,23).

Schlussfolgerung

In dieser retrospektiven Analyse wies Ribociclib + NSAI + OFS klare Vorteile in Bezug auf alle Effektivitätsendpunkte einschließlich des GÜ bei prämenopausalen Frauen mit HR+/HER2− Brustkrebs im Frühstadium auf, ohne dass die allgemeinen Behandlungsabbruchraten verglichen mit Tamoxifen ± OFS anstiegen.

Keywords

ribociclib - indirect treatment comparison - HR-positive - HER2-negative - early breast cancer

Schlüsselwörter

Ribociclib - indirekter Behandlungsvergleich - HR-positiv - HER2-negativ - Brustkrebs im Frühstadium

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