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DOI: 10.1055/a-2622-0684
Update Gynecologic Malignancies 2025 – Expert Opinion on Systemic Therapy for Early and Advanced Gynecological Cancers
Update gynäkologische Tumoren 2025 – Expertenmeinung zur systemischen Therapie für die Behandlung von frühen und fortgeschrittenen gynäkologischen Tumoren
Abstract
There have been major changes in the understanding of gynecologic malignancies in
recent years, leading to new therapy options and subsequently to greater responsibilities
for every professional treating those patients. The most significant therapeutic advances
were achieved with checkpoint inhibitors (CPI), especially for endometrial and cervical
cancer. In ovarian cancer the dominant and most important new substances are poly
(ADP-ribose) polymerase inhibitors (PARPi). This review aims to summarize the latest
studies and developments in the therapeutic landscape of endometrial, ovarian, and
cervical cancer. The treatment of advanced endometrial cancer has changed significantly
with the introduction of CPI such as dostarlimab (RUBY trial), durvalumab (DUO-E trial)
and pembrolizumab (Keynote-868 trial). For ovarian cancer PARPi have shown substantial
PFS benefits in key approval trials, including PRIMA for niraparib, PAOLA for olaparib,
and ATHENA-MONO for rucaparib. These findings have established PARPi as the standard
of care in maintenance therapy. Overall survival (OS) data for PRIMA and PAOLA are
now available and are analyzed and placed into context in this article. Furthermore,
mirvetuximab soravtansine is the first antibody-drug conjugate (ADC) approved in Germany
for platinum-resistant ovarian cancer for patients with folate receptor alpha expression.
The Keynote-A18 and BEATcc trials have opened new options for the utilization of immuno-oncology
in cervical cancer treatment. Along with new therapeutic options, new biomarkers have
also become part of daily clinical practice as predictive and prognostic factors as
well as forming the basis for targeted personalized medicine.
The use of CPI is revolutionizing the treatment of all gynecologic cancers and offers
significant benefits for progression-free survival (PFS) and OS in most therapy regimens.
With the increased use of ADCs, this is not the end of these developments. Therapy
algorithms from a certified German oncology center are developed and presented in
this article.
Zusammenfassung
In den letzten Jahren gab es wichtige Änderungen im Verständnis von gynäkologischen
Tumoren, die in neue Therapieoptionen mündeten und eine größere Verantwortung für
alle in der Behandlung dieser Patientinnen involvierten medizinischen Fachkräfte bedeuten.
Zu den wichtigsten therapeutischen Fortschritten, besonders für die Behandlung von
Endometrium- und Gebärmutterhalskrebs, gehören die sog. Checkpoint-Inhibitoren (CPI).
Die wichtigsten neuen Substanzen, die zur Behandlung des Ovarialkarzinoms eingesetzt
werden, sind Poly(ADP-ribose)-Polymerasen-Inhibitoren (PARPi). Ziel dieses Übersichtsartikels
ist, eine Zusammenfassung der neuesten Studien und Entwicklungen in der therapeutischen
Landschaft der Endometrium-, Ovarial- und Zervixkarzinome zu geben. Die Behandlung
des fortgeschrittenen Endometriumkarzinoms hat sich durch die Einführung von CPI wie
Dostarlimab (RUBY-Studie), Durvalumab (DUO-E-Studie) und Pembrolizumab (Keynote-868-Studie)
substanziell verändert. Beim Ovarialkarzinom haben wichtige Zulassungsstudien, darunter
PRIMA für Niraparib, PAOLA für Olaparib und ATHENA-MONO für Rucaparib, gezeigt, dass
PARPi mit wesentlichen Progressionsfreien-Überlebens-(PFÜ-)Vorteilen behaftet sind.
Diese Ergebnisse haben PARPi als neuen Therapiestandard bei der Erhaltungstherapie
etabliert. Die Gesamtüberlebens-(GÜ-)Daten der PRIMA- und PAOLA-Studien sind jetzt
vorliegend und werden hier analysiert und kontextualisiert. Darüber hinaus wurde Mirvetuximab-Soravtansin
als erstes Antikörper-Wirkstoff-Konjugat (AWK) für die Behandlung von Patientinnen
mit platinresistenten Ovarialkarzinomen, die den Folatrezeptor alpha exprimieren,
in Deutschland zugelassen. Die Keynote-A18- und BEATcc-Studien haben neue Möglichkeiten
für den Einsatz von Immunonkologie bei der Behandlung von Zervixkarzinomen eröffnet.
Zusammen mit diesen neuen therapeutischen Optionen gibt es nun auch neue Biomarker,
die als prädiktive und prognostische Faktoren in die klinische Praxis eingegangen
sind und nun die Basis einer gezielten individualisierten Medizin bilden.
Der Einsatz von CPI hat die Therapie aller gynäkologischen Karzinome revolutioniert.
In den meisten Therapieregimes weisen CPI erhebliche Vorteile beim PFÜ und GÜ auf.
Mit der allmählichen Einführung von AWKs ist das Ende dieser Entwicklung noch nicht
erreicht. Behandlungsalgorithmen aus einem zertifizierten deutschen Krebszentrum werden
entwickelt und in diesem Artikel vorgestellt.
Keywords
gynecologic malignancies - endometrial cancer - ovarian cancer - cervical cancer - immune oncologySchlüsselwörter
gynäkologische Tumoren - Endometriumkarzinom - Ovarialkarzinom - Zervixkarzinom - ImmunonkologiePublikationsverlauf
Eingereicht: 24. März 2025
Angenommen nach Revision: 24. Mai 2025
Artikel online veröffentlicht:
30. Juni 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1 McCormack M, Eminowicz G, Gallardo D. et al. Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial. Lancet 2024; 404: 1525-1535
- 2 Lorusso D, Xiang Y, Hasegawa K. et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet 2024; 403: 1341-1350
- 3 FDA. FDA approves pembrolizumab with chemoradiotherapy for FIGO 2014 Stage III–IVA cervical cancer. 09.08.2024 Zugriff am 02. Januar 2025 unter: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemoradiotherapy-figo-2014-stage-iii-iva-cervical-cancer
- 4 European Medicines Agency. Keytruda – opinion on variation to marketing authorisation | European Medicines Agency (EMA). 01.01.2025 Zugriff am 02. Januar 2025 unter: https://www.ema.europa.eu/en/medicines/human/variation/keytruda-1
- 5 Oaknin A, Gladieff L, Martínez-García J. et al. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet 2024; 403: 31-43
- 6 Fehm T, Stübs FA, Koch MC. et al. Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities. Geburtshilfe Frauenheilkd 2022; 82: 181-205
- 7 van Gorp T, Cibula D, Lv W. et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol 2024; 35: 968-980
- 8 Tempfer C, Brucker S, Juhasz-Boess I. et al. Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on the Use of Primary Chemoimmunotherapy to Treat Patients with Locally Advanced or Recurrent Endometrial Cancer. Geburtshilfe Frauenheilkd 2023; 83: 1095-1101
- 9 Mirza MR, Chase DM, Slomovitz BM. et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med 2023; 388: 2145-2158
- 10 Westin SN, Moore K, Chon HS. et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol 2024; 42: 283-299
- 11 Eskander RN, Sill MW, Beffa L. et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med 2023; 388: 2159-2170
- 12 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Endometriumkarzinom. AWMF-Registernummer: 032–034OL. 3. Aufl.;. 2024 Zugriff am 30. Juni 2024 unter: https://register.awmf.org/de/leitlinien/detail/032-034OL
- 13 Mirza MR, Bjørge L, Marmé F. et al. Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial. Gynecol Oncol 2024; 192: 128-136
- 14 Meric-Bernstam F, Makker V, Oaknin A. et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol 2024; 42: 47-58
- 15 Monk BJ, Barretina-Ginesta MP, Pothuri B. et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol 2024; 35: 981-992
- 16 Ray-Coquard I, Leary A, Pignata S. et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol 2023; 34: 681-692
- 17 Monk BJ, Coleman RL, Fujiwara K. et al. ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. Int J Gynecol Cancer 2021; 31: 1589-1594
- 18 Trillsch F, Okamoto A, Kim J-W. et al. 43O Durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) for newly diagnosed advanced ovarian cancer (AOC) without a tumour BRCA1/BRCA2 mutation (non-tBRCAm): Updated results from DUO-O. ESMO Open 2024; 9: 103550
- 19 Janjigian YY, Oaknin A, Lang JM. et al. TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumors. JCO 2023; 41: TPS3153
- 20 Monk BJ, Parkinson C, Lim MC. et al. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol 2022; 40: 3952-3964
- 21 Lorusso D, Guy H, Samyshkin Y. et al. Feasibility Study of a Network Meta-Analysis and Unanchored Population-Adjusted Indirect Treatment Comparison of Niraparib, Olaparib, and Bevacizumab as Maintenance Therapies in Patients with Newly Diagnosed Advanced Ovarian Cancer. Cancers (Basel) 2022; 14: 1285
- 22 Wang H, Wu M, Liu H. et al. Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis. Front Oncol 2021; 11: 785102