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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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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Tumour-derived organoids and future clinical applications

BJMO - volume 15, issue 2, march 2021

S. Dumont MD, T. Van Gorp MD, PhD, I. Vergote MD, PhD, D. Timmerman MD, PhD

SUMMARY

Human drug research, and cancer drug research in particular, heavily relies on traditional tumour models such as 2D cell cultures and xenografts to develop and test novel therapeutics. Organoids are a novel 3D cell platform derived from stem cells, allowing to faithfully replicate human tissue in an in vitro environment, bridging the ease of use of 2D cell cultures and the biological relevance of xenografts. In this manuscript, we introduce organoids to the oncological community and demonstrate the major advantages and challenges of this exciting new technology. Cancer organoids could be the next major step in tumour research and drug development, ultimately leading to highly precise personalised medicine.

(BELG J MED ONCOL 2021;15(2):63-8)

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Highlights in gynaecological cancers

BJMO - volume 14, issue 5, september 2020

J. Blokken PhD, PharmD, Tom Feys MBA, MSc, I. Vergote MD, PhD

Summary

The highlights in gynaecologic cancers from ASCO 2020 include data on the role of secondary cytoreductive surgery for women with recurrent ovarian cancer as well as several abstracts on the use of PARP-inhibitors in patients with platinum-sensitive relapsed ovarian cancer. In addition, several presentations focused on novel therapeutic strategies for patients with ovarian cancer, including immune-checkpoint inhibitors and the antibody-drug conjugate mirvetuximab soravtansine. Finally, the effectivity of sequential chemoradiation and the combination of the anti-PD1 antibody camrelizumab with the VEGF-targeting agent apatinib in patients with cervical cancer will be discussed.

(BELG J MED ONCOL 2020;14(5):227-32)

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P.09 Tamoxifen metabolism and breast cancer efficacy in the neo-adjuvant or metastatic setting – a prospective multicenter trial

BJMO - 2017, issue 3, february 2017

L. Jongen , P. Neven MD, PhD, A. Lintermans , K. Van Asten MSc, C. Blomme , D. Lambrechts PhD, A. Poppe , H. Wildiers MD, PhD, A.S. Dieudonné , J. Decloedt MD, P. Berteloot , D. Verhoeven MD, PhD, M. Joerger , P. Vuylsteke MD, W. Wynendaele MD, PhD, M. Casteels , Sabine Van Huffel , W. Lybaert MD, J. Van Ginderachter , R. Paridaens , I. Vergote MD, PhD, V. Dezentjé , B. Van Calster PhD, H-J. Guchelaar

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Therapy-orienting testing of BRCA1 and BRCA2 germline mutations in women with ovarian cancer

BJMO - volume 9, issue 2, may 2015

K. Claes PhD, H. Denys MD, PhD, M. Huizing MD, PhD, I. Vergote MD, PhD, F. Kridelka MD, PhD, J. De Grève MD, PhD, V. Bours MD, PhD, On behalf of the BRCA Testing Working Group.

With the aim to optimally position poly-(adenosine diphosphate-ribose) polymerase inhibitors in the treatment of ovarian cancer, a panel of Belgian Experts came to a national multidisciplinary consensus: (i) germline BRCA1/2 testing should be indicated for all women with high-grade serous epithelial ovarian cancer, who are in good general condition (i.e. eligible for systemic treatment with low toxicity); BRCA1/2 mutation detection ratios being about 15–20% in this group; (ii) as the finding of a BRCA1/2 germline mutation has therapeutic implications in ovarian cancer patients, the request for therapy-orienting testing should be made as soon as possible during the course of first-line treatment. Pre-test genetic counselling is important because positive testing has implications for both the patients and their relatives, and the nature of the discussions depends on whether they take place in a therapeutic or familial context. The organisation of consultations should be coordinated in a collaborative effort between clinical geneticists, and gynaecological and medical oncologists, keeping in mind that ‘fast-track’ pre-test genetic counselling and short turnaround times are required for patients for whom the test results will have a therapeutic impact. Offering germline BRCA1/2 testing to all patients with high-grade serous epithelial ovarian cancer who are eligible for systemic treatment with low toxicity will lead to a limited increase in the number of patients eligible for this test in Belgium.

(BELG J MED ONCOL 2015;9(2):65–70)

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