J.F. Baurain MD, PhD

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)

Guidance for the prevention and treatment of venous thromboembolism in cancer patients

Summary

Venous thrombosis is a common complication in cancer patients and thromboembolism is the second most common cause of death. Several practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, these guidelines do not sufficiently cover commonly encountered clinical challenges. With this expert panel, consisting of medical oncologists, haematologists, internists and thrombosis specialists, we aimed to develop a practical Belgian guidance for adequate prevention and treatment of cancer-associated thrombosis that covered several challenging situations encountered in daily clinic. This paper discusses the following topics: type and treatment duration of anticoagulant therapy, recurrent VTE despite anticoagulation, anticoagulation in case of renal impairment, liver disease and thrombocytopenia, the role of anti-Xa monitoring, central venous catheter-associated thrombosis, the position of direct oral anticoagulants and thromboprophylaxis, both in ambulatory and hospitalised patients. For an overview of the recommendations formulated by the expert panel, we refer to the key messages for clinical practice in this article.

(BELG J MED ONCOL 2016;10(7):249–255)

How immune checkpoint inhibition reshaped advanced melanoma

Cutaneous melanoma has long been one of the most aggressive forms of cancer, with limited treatment options and a very dismal prognosis. However, in recent years new strategies for treating melanoma have been introduced that significantly improve the outlook for patients with this challenging disease. One of the most important advances has been the development of immunotherapy. The better understanding of the role of the immunological system in tumor control has paved the way for strategies to enhance the immune response against cancer cells. Monoclonal antibodies (mAbs) against the immune checkpoints cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have demonstrated high activity in melanoma and other tumors. This has marked a new era in the treatment of metastatic melanoma and much research is now ongoing with other checkpoint inhibitors and investigating combinations of agents targeting different immune checkpoints.

Adjuvant treatment for uterine cancers, a review of the current evidence

Summary

To date, the main treatment of loco-regional uterine cancer is surgery. The benefit of adjuvant treatment depends on the subtype of cancer, stage, and risk factors. We describe here the current evidence-based data supporting the administration of adjuvant treatment after surgery, with a focus on chemotherapy.

(BELG J MED ONCOL 2016;10(2):63–68)

Highlights in melanoma

(BELG J MED ONCOL 2015;9:132–8)