Articles

Immunotherapy for advanced endometrial carcinoma: Time for a paradigm shift?

BJMO - volume 18, issue 2, march 2024

C. Gennigens MD, PhD, S. Altintas MD, PhD, J-F. Baurain MD, PhD, H. Denys MD, PhD, S. Henry MD, I. Vergote MD, PhD, T. Van Gorp MD, PhD

SUMMARY

Over the past decade, immune checkpoint inhibitors (ICI) emerged as a new therapeutic pillar across a broad range of cancer types. An important characteristic of patients responding to ICI-based therapy consists of a high mutational burden in the tumours. In line with this, patients with microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) endometrial cancer (EC) proved to be particularly sensitive to ICI, leading to the approval of anti-PD-1 antibodies for patients with MSI-H/dMMR ≥2nd line recurrent setting. Responses to single-agent ICI have also been reported in a small proportion of patients with microsatellite stable (MSS) EC. However, a high unmet need remains for these patients. More recently, several phase III randomised controlled trials showed that adding an ICI to standard chemotherapy significantly delays the disease progression in patients with primary advanced or recurrent MSI-H/dMMR EC, but also, to a lesser extent, in MMR proficient (p)/MSS EC. This article will briefly review the available clinical trial data with ICI-based therapies in EC and will assess how this treatment modality could be integrated into the Belgian treatment paradigm for these patients.

(BELG J MED ONCOL 2024;18(2):49–59)

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Value of testing for homologous recombination repair deficiency in newly diagnosed advanced-stage epithelial ovarian cancer: Recommendations for Belgian physicians

BJMO - volume 17, issue 2, march 2023

C. Gennigens MD, PhD, H. Denys MD, PhD, S. Altintas MD, PhD, J. Kerger MD, J-F. Baurain MD, PhD, V. Bours MD, PhD, S. Henry MD, K. Van de Vijver MD, PhD, D. Lambrechts PhD, I. Vergote MD, PhD

SUMMARY

Epithelial ovarian cancer (EOC) is the most frequent form of OC, a disease with a poor prognosis and high lethality, as most patients are diagnosed at advanced stages. To successfully battle EOC, it is crucial to identify reliable biomarkers and use personalised therapies in patient subgroups. A common feature of high-grade serous and endometrioid OC is homologous recombination repair deficiency (HRD), which frequently stems from the inactivation of the breast cancer susceptibility (BRCA) genes. Poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) were, therefore, developed for their lethality against HRD tumour cells. While patients with non-HRD tumours may also benefit from PARPi therapy in the recurrent EOC setting, recent phase III trials on newly diagnosed advanced-stage EOC have shown that PARPi treatment benefit is greater in patients with HRD tumours. These findings open new avenues for the use of PARPi as maintenance therapy in HRD-positive patients who had received first-line chemotherapy. This manuscript provides recommendations for Belgian physicians on how to approach HRD testing and incorporate it into treatment decisions of patients with newly diagnosed advanced-stage EOC.

(BELG J MED ONCOL 2023;17(2):38–45)

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Immune cell and extracellular vesicle-based biomarkers for gynaecologic cancers

BJMO - volume 17, issue 2, march 2023

L. Lippens PhD, K. Vandecasteele MD, PhD, A. Hendrix PhD, H. Denys MD, PhD

SUMMARY

Immune checkpoint blockade has shown great potential in oncology. However, only a fraction of patients benefits from this therapy. Furthermore, severe immune-related adverse events occur in a part of the patients, and financial toxicity cannot be underestimated. It is therefore important to develop predictive biomarkers to differentiate responders from non-responders. Tumour tissue samples offer a large amount of information as anti-tumour immunity is regulated through multiple factors in the tumour microenvironment. The potential of tumour-infiltrating immune cells was investigated to predict response to therapy and survival. In contrast to tissue biopsies, liquid biopsies allow for collection in a less invasive manner, allow for repetitive sampling during therapy, and offer information on all cancer cells in the tumour as well as metastases at distinct locations in the body. Extracellular vesicles (EVs) present in the circulation are a spatiotemporal fingerprint of the cell of origin. Therefore, EV-derived information has the potential to be used for diagnosis, prognosis, treatment selection and evaluating treatment response. However, the clinical application of EVs is currently hampered by a lack of sensitive, high-throughput and fast EV analysis techniques.

(BELG J MED ONCOL 2023;17(2):63–5)

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Belgian clinical practice guidelines for the treatment of patients with HER2-positive advanced breast cancer

BJMO - volume 16, issue 6, october 2022

G. Nader-Marta MD, F.P. Duhoux MD, PhD, D. Taylor MD, T. Van den Mooter MD, H. Denys MD, PhD, J-L. Canon MD, J. Mebis MD, A. Awada MD, PhD, H. Wildiers MD, PhD, K. Punie MD, E. de Azambuja MD, PhD

SUMMARY

HER2-targeted agents are the central component of HER2-positive metastatic breast cancer (MBC) treatment. The combination of trastuzumab, pertuzumab and a taxane is the preferred first-line regimen in most settings. For patients with disease relapse after adjuvant therapy, treatment decisions in the first-line are influenced by the treatment-free interval and the regimens used in the (neo)adjuvant setting. T-DXd has been recently established as the preferred second-line therapy. T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are reasonable third-line options, although efficacy and safety data of these regimens after prior exposure to T-DXd are lacking. In fourth and later lines, trastuzumab duocarmazine, neratinib plus capecitabine, margetuximab plus chemotherapy, lapatinib-based combinations or the continuation of trastuzumab with different chemotherapy partners are valid alternatives.

(BELG J MED ONCOL 2022;16(6): 287–92)

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Standard of care in 2021 for patients with ovarian cancer in Belgium

BJMO - volume 15, issue 6, october 2021

I. Vergote MD, PhD, H. Denys MD, PhD, J. De Grève MD, PhD, C. Gennigens MD, PhD, K. Van de Vijver MD, PhD, J. Kerger MD, P. Vuylsteke MD, J-F. Baurain MD, PhD

SUMMARY

Ovarian cancer is often diagnosed at an advanced stage, which is associated with worse survival outcomes and more limited therapeutic options. Over the last years, knowledge regarding the molecular features of ovarian cancer has advanced considerably, enabling the development of several options for diagnosis and treatment in a patient-tailored approach. Identification of homologous recombination deficiency (such as mutations of the BRCA1 and BRCA2 genes, or genomic instability) affecting DNA repair, has become essential in guiding treatment decisions, especially after the development of targeted agents. Therapeutic decisions take into consideration the cancer subtype, its molecular features and disease stage. Fundamental principles of good treatment for women with ovarian cancer include debulking surgery (to reduce the tumour to no residual disease whenever possible), along with appropriate systemic treatment (chemotherapy and targeted agents). To aid Belgian physicians in developing the best individual medical strategies for patients with primary and recurrent ovarian cancer, we present here standard of care applicable in Belgium, that also includes recently developed targeted agents and currently applicable reimbursement criteria.

(BELG J MED ONCOL 2021;15(6):286-91)

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Clinical management of first-line advanced triple-negative breast cancer patients

BJMO - volume 14, issue 7, november 2020

M. Rediti MD, K. Punie MD, E. de Azambuja MD, PhD, E. Naert MD, D. Taylor MD, FP. Duhoux MD, PhD, H. Denys MD, PhD, A. Awada MD, PhD, H. Wildiers MD, PhD, M. Ignatiadis MD, PhD

SUMMARY

Chemotherapy has represented the main treatment option for patients with advanced triple-negative breast cancer for a long time. However, due to our better understanding of tumour biology, recent clinical trials led to a change in the treatment paradigm of this disease, identifying clinically relevant subgroups with different therapeutic options. Both clinical and biological factors have become relevant and need to be considered in the treatment decision algorithm of this heterogeneous disease.

(BELG J MED ONCOL 2020;14(7):333-38)

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Algorithms for molecular testing in solid tumours

BJMO - volume 13, issue 7, november 2019

Ir A. Hébrant PhD, M. Lammens MD, PhD, C. Van den Broecke MD, N. D’Haene MD, PhD, J. Van den Oord MD, PhD, A. Vanderstichele MD, PhD, A. Dendooven MD, PhD, P. Neven MD, PhD, K. Punie MD, G. Floris MD, PhD, J. Van der Meulen MD, HA. Poirel MD, PhD, C. Dooms MD, PhD, S. Rottey MD, PhD, T. Boterberg MD, PhD, L. Brochez MD, PhD, M.C. Burlacu MD, G. Costante MD, D. Creytens MD, PhD, P. De Paepe MD, PhD, R. De Pauwn MD, B. Decallonne MD, PhD, F. Dedeurwaerdere MD, H. Denys MD, PhD, L. Ferdinande MD, PhD, R. Forsyth MD, PhD, M. Garmyn MD, PhD, T. Gevaert MD, PhD, J. De Grève MD, PhD, E. Govaerts MD, E. Hauben MD, PhD, J. Kerger MD, O. Kholmanskikh Van Criekingen MD, PhD, V. Kruse MD, PhD, Y. Lalami MD, L. Lapeire MD, PhD, P. Lefesvre MD, PhD, J.P. Machiels MD, PhD, B. Maes MD, PhD, G. Martens MD, PhD, M. Remmelink MD, PhD, I. Salmon MD, PhD, R. Sciot MD, PhD, S. Tejpar MD, PhD, K. Van de Vijver MD, PhD, L. Van de Voorde MD, I. Van den Berghe MD, A. Van den Bruel MD, K. Vandecasteele MD, PhD, L. Vanwalleghem MD, K. Vermaelen MD, PhD, R. Salgado MD, PhD, E. Wauters MD, PhD, B. Weynand MD, PhD, E. Van Valckenborgh PhD, G. Raicevic PhD, M. Van den Bulcke PhD, P. Pauwels MD, PhD

SUMMARY

In order to advise the Federal Government on the reimbursement of molecular tests related to Personalised Medicine in Oncology, the Commission of Personalised Medicine (ComPerMed), represented by Belgian experts, has developed a methodology to classify molecular testing in oncology. The different molecular tests per cancer type are represented in algorithms and are annotated with a test level reflecting their relevance based on current guidelines, drug approvals and clinical data. The molecular tests are documented with recent literature, guidelines and a brief technical description. This methodology was applied on different solid tumours for which molecular testing is a clear clinical need.

(BELG J MED ONCOL 2019;13(7):286–95)

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