Endokrine Therapielandschaft bei Patient*innen mit HR+ HER2− frühem Mammakarzinom in Deutschland vor Einführung der CDK4/6-Inhibitor-Behandlung – eine Real-World-Analyse

Zusammenfassung

Einleitung Während prämenopausale Patientinnen mit einem HR+ HER2− frühen Mammakarzinom mit Tamoxifen +/− ovarielle Suppression mit einem GnRH-Analogon oder einem Aromataseinhibitor (AI) + GnRH behandelt werden, erhalten postmenopausale Frauen vorwiegend einen AI aufgrund der besseren Wirksamkeit verglichen mit Tamoxifen. Da es durch den Einzug der CDK4/6-Inhibitoren in die Behandlung des frühen Mammakarzinoms mit höherem Rückfallrisiko vermutlich zu einer Verschiebung der endokrinen Therapielandschaft kommt, ist von Interesse, wie in Deutschland potenzielle CDK4/6-Inhibitor-Kandidat*innen vor deren Markteinführung behandelt wurden.

Patienten und Methoden Im Rahmen einer retrospektiven, multizentrischen Analyse wurden anonymisierte Daten von Patient*innen mit einem HR+ HER2− frühen Mammakarzinom und einer im Zeitraum zwischen 10/2021–03/2022 begonnenen Antihormontherapie erhoben. Potenzielle CDK4/6-Inhibitor-Kandidat*innen wurden anhand der Einschlusskriterien der NATALEE- und monarchE-Studien in entsprechende Risikokollektive unterteilt.

Ergebnisse Insgesamt wurden Daten von 238 Patient*innen aus 29 Zentren analysiert. Während den monarchE-Kriterien 20,6 % der Patient*innen zugeordnet werden konnten, enthielt das NATALEE-ähnliche Kollektiv 46,2 % der Patient*innen. 53,8 % der Patient*innen erfüllten weder die Einschlusskriterien der NATALEE- noch die der monarchE-Studie. Über die Hälfte der Patient*innen erhielt keine Chemotherapie. Im Gesamtkollektiv waren 28,6 % der Patientinnen prämenopausal. 67,6 % der prämenopausalen Frauen wurden mit einer neo-/adjuvanten Chemotherapie behandelt. 61,8 % der prämenopausalen Patientinnen erhielten als adjuvante Antihormontherapie Tamoxifen, 19,1 % AI + GnRH und 10,3 % Tamoxifen + GnRH.

Schlussfolgerung Trotz des hohen Anteils prämenopausaler Patientinnen, die mit einer aggressiven Therapie im Sinne einer Chemotherapie behandelt wurden, wurde bei nur einem Drittel der prämenopausalen Patientinnen GnRH zur Antihormontherapie hinzugenommen. Untersuchungen zu einem späteren Zeitpunkt sowie Registerstudien sind nötig, um zu sehen, wie sich durch den Einzug der CDK4/6-Inhibitoren die endokrine Therapielandschaft in Deutschland verändert.

Abstract

Introduction While premenopausal patients with HR+ HER2− early breast cancer are treated with tamoxifen +/− ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority of postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of earlystage breast cancer with a higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany receive before CDK4/6 inhibitors were available.

Patients and Methods As part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2− early-stage breast cancer who received endocrine therapy in the period between 10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials.

Results The data of 238 patients from 29 different centers were analyzed. While 20.6 % of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of 46.2 % of patients. 53.8 % of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6 % of patients in the whole cohort were premenopausal. 67.6 % of premenopausal women received neo-/adjuvant chemotherapy. 61.8 % of premenopausal patients received tamoxifen as adjuvant endocrine therapy, 19.1 % received an AI + GnRH and 10.3 % were treated with tamoxifen + GnRH.

Conclusion Despite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed following the introduction of CDK4/6 inhibitors.

Schlüsselwörter

Brustkrebs - Mammakarzinom - Antihormontherapie - GnRH - Tamoxifen - Aromataseinhibitor

Key words

breast cancer - endocrine treatment - OFS - tamoxifen - aromatase inhibitor

• Literatur

• 1 Ditsch N, Wocke A, Untch M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2022. Breast Care (Basel) 2022; 17: 403-420
• 2 Thomssen C, Balic M, Harbeck N. et al. St. Gallen/Vienna 2021: A Brief Summary of the Consensus Discussion on Customizing Therapies for Women with Early Breast Cancer. Breast Care (Basel) 2021; 16: 135-143
• 3 Paluch-Shimon S, Lueck H, Beith J. et al. 153P Adjuvant endocrine therapy combined with abemaciclib in monarchE patients with high-risk early breast cancer: Disease characteristics and endocrine therapy choice by menopausal status. Ann Oncol 2021; 32: S427-S428
• 4 Tarantino P. Consensus statement regarding use of adjuvant abemaciclib in patients with early-stage hormone-receptors positive breast cancer. Boston, MA: Dana-Farber Cancer Institute; 2021
• 5 Novartis. Novartis Kisqali® Phase III NATALEE trial meets primary endpoint at interim analysis demonstrating clinically meaningful benefit in broad population of patients with early breast cancer. 27.03.2023. Zugriff am 27. März 2023 unter. https://www.novartis.com/news/mediareleases/novartis-kisqali-phase-iii-natalee-trial-meets-primary-endpointinterim-analysis-demonstrating-clinically-meaningful-benefit-broadpopulation-patients-early-breast-cancer
• 6 Tripathy D, Im SA, Colleoni M. et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 2018; 19: 904-915
• 7 ClinicalTrials.gov. Zugriff am 01. Dezember 2022 unter. https://clinicaltrials.gov/
• 8 Heer E, Harper A, Escandor N. et al. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. Lancet Glob Health 2020; 8: e1027-e1037
• 9 Johnston SRD, Harbeck N, Hegg R. et al. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol 2020; 38: 3987-3998
• 10 Wockel A, Festl J, Stuber T. et al. Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2018; 78: 1056-1088
• 11 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
• 12 Pagani O, Francis PA, Fleming GF. et al. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol 2020; 38: 1293-1303
• 13 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol 2022; 23: 382-392
• 14 Pagani O, Walley BA, Fleming GF. et al. Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. J Clin Oncol 2023; 41: 1376-1382
• 15 Regan MM, Neven P, Giobbie-Hurder A. et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1–98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol 2011; 12: 1101-1108
• 16 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level metaanalysis of the randomised trials. Lancet 2015; 386: 1341-1352
• 17 Baum M, Budzar AU, Cuzick J. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139