J-F. Baurain MD, PhD

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

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)

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

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)

Is there a place for thromboprophylaxis in cancer patients?

SUMMARY

Venous thromboembolism (VTE) is common in cancer patients. It is associated with poor outcomes and increased mortality. In fact, VTE is known as the second most common cause of mortality in cancer patients. Although the benefit of thromboprophylaxis is clear for acutely ill hospitalised cancer patients, routine prophylaxis is not recommended for all ambulatory cancer patients. The reason is the risk to treat a high proportion of patients who do not need treatment and an increased risk of major bleeding. Here we highlight the importance of adequate risk assessment models to select patients at an increased VTE risk and present pivotal trial results that form the basis for the latest international treatment guidelines related to thromboprophylaxis in cancer patients.

(BELG J MED ONCOL 2022;16(2):53–9)

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

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)

Immuno-oncology combinations: rationale and clinical implications in melanoma, renal cell carcinoma and lung cancer

ABSTRACT

Over the past years, immune checkpoint inhibitors have been widely used for the treatment of a broad range of malignancies. Unfortunately, only a proportion of patients derives long-term benefit from these therapeutics. In fact, a majority of patients fails to respond to immune checkpoint inhibition, while others relapse after a certain time. In an attempt to increase the response rate of tumours to these drugs, investigators have looked into the potential of combining different immunotherapeutic agents. Since inhibitors of the immune checkpoints CTLA-4 and PD-(L)1 have different modes of action and given the fact that blocking one of both pathways results in an upregulation of the other, provide a theoretical rationale to combine these agents. This review provides an overview of clinical studies evaluating combinations of CTLA-4 and PD-(L)1 inhibitors in the treatment of melanoma, renal cell carcinoma and non-small-cell lung cancer.

The role of direct oral anticoagulants in the management of cancer-associated thrombosis

SUMMARY

Cancer patients are at an increased risk of venous thromboembolism (VTE). The current standard initial treatment of an acute episode of VTE in cancer patients consists of the administration of three to six months of subcutaneous low molecular weight heparin (LMWH) at a dose adjusted to the body weight. The efficacy and safety profile of LMWHs are well established, but a drawback of these agents is that they require daily subcutaneous administration. In addition, they are mainly cleared through the kidneys, and their use in patients with severe renal insufficiency may require dose reduction or monitoring of the anti-Xa activity. To address the issues with LMWH, several direct oral anticoagulants (DOAC) have been developed for the treatment of VTE. In contrast to LMWHs and vitamin K antagonist, DOACs directly interfere with thrombin or activated factor X (FXa). DOACs have now become standard treatment options in the general management of VTE, but until recently, there were no results of clinical trials specifically assessing the role of DOACs in the treatment of cancer-associated thrombosis. Recently, the Hokusai VTE cancer study and preliminary data from the Select-D trial demonstrated that DOACs are non-inferior to LMWH in preventing recurrent VTE. However, both studies also show that this comes at the cost of an increased rate of both major and clinically-relevant non-major bleeding. Especially in the subgroup of patients with gastrointestinal cancer, the benefit in VTE recurrence with the DOAC seems to be outbalanced by a significantly increased bleeding risk. Based on the available results, DOACs might represent an interesting alternative for LMWH in certain subgroups of patients, but with an important list of exceptions. It seems reasonable not to use DOACs in patients with a high bleeding risk, and especially in patients with gastrointestinal cancer, DOACs should not be the first-line choice. In summary, while LMWHs are currently the standard of care in the acute management of cancer-associated thrombosis, the advent of DOACs is welcomed for patients at a low bleeding risk who are in need of long-term anticoagulation.

(BELG J MED ONCOL 2019;13(2):46–53)

Screening for occult cancer in patients with unprovoked venous thromboembolism: Belgian expert guidance

Unprovoked venous thromboembolism (VTE) may be the earliest sign of malignancy, and as a result, screening for occult cancer in these patients has become routine practice. However, the elaborateness of this screening is subject to debate and varies between medical centres. This study’s expert panel, consisting of oncologists and thrombosis specialists, aimed to develop a practical Belgian guidance for adequate cancer screening in patients with unprovoked VTE. In summary, comprehensive non-invasive cancer screening consisting of a medical history assessment, physical examinations, basic blood tests and a chest X-ray is sufficient to pick up the vast majority of occult cancers. When specific abnormalities are picked up by the battery of tests in the comprehensive non-invasive cancer screening, more extensive screening using CT scans are recommended. Routine CT screening in all patients presenting with an unprovoked VTE does not provide a significant clinical benefit and should not be routinely performed. In the presence of specific risk factors (e.g., older age, smoking history, previous VTE), physicians are advised to be more vigilant. Finally, given the significant anxiety that cancer screening may cause to patients, accurate and clear patient communication is key. A complete list of guidance statements is provided at the end of the article.

(BELG J MED ONCOL 2018;12(7):326–329)