PHARMACOTHERAPY

Precision therapy in pancreaticobiliary cancers: molecular testing for all?

BJMO - volume 14, issue 6, october 2020

J-L. van Laethem MD, PhD, L. Mans MD, A. Demols MD, PhD

SUMMARY

Pancreaticobiliary cancers remain challenging to be treated due to aggressive biology and heterogeneous molecular patterns. Chemotherapy remains the backbone therapy, with two lines available in each cancer. Using targeted therapies in unselected populations has led to complete failure while currently used immunotherapy with anti-PD1 can only be active in instable tumours (MSI-High), a rare condition in these cancers. As recently reported, targeting specific genes in pancreaticobiliary cancers may significantly improve tumour control and offer new ways to manage them, in addition to conventional chemotherapies usually proposed in front line. Consequently, it is now more and more recommended to perform genetic and genomic testing of these tumours, searching for new druggable targets. Dedicated trials focusing on such enriched populations are currently ongoing.

(BELG J MED ONCOL 2020;14(6):274-9)

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Optimal treatment of metastatic gastric and gastro-oesophageal junction adenocarcinoma

BJMO - volume 14, issue 4, june 2020

J. Siplet MD, A. De Cuyper MD, M. van den Eynde MD, PhD

SUMMARY

Standard of care for advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma relies on palliative systemic therapy that can improve both survival and quality of life of patients. In first-line, platinum – fluoropyrimidine-based doublet (combined with trastuzumab for HER2/neu positive tumours) or triplet chemotherapy regimen (mainly combining a taxane) is now standard option. For fit patients, a secondline with taxane and/or ramucirumab or irinotecan monotherapy, is an option. Latest studies showed interest for new treatments such as immune checkpoint inhibitors (anti-PD-1) or trifluridine/tipiracil in some situations.

(BELG J MED ONCOL 2020;14(4):146–50)

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Appropriateness of treatment options in patients with metastatic castrationresistant prostate cancer with a focus on radium-223: outcomes of a Belgian multidisciplinary Consensus Meeting

BJMO - volume 13, issue 6, october 2019

P. Ost MD, PhD, D. Schrijvers MD, PhD, L. Duck MD, M. Gizzi MD, K. Goffin MD, PhD, S. Joniau MD, PhD, S. Rottey MD, PhD, T. Roumeguère MD, PhD, E. Seront MD, PhD, N. Withofs MD, PhD, B. Tombal MD, PhD

SUMMARY

The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the approval of a variety of therapeutic agents including abiraterone acetate, cabazitaxel, docetaxel, enzalutamide and radium-223 dichloride and the introduction of docetaxel and abiraterone acetate in combination with androgen deprivation therapy in newly diagnosed metastatic prostate cancer. Evidence on the optimal sequence of these therapies is scarce. In practice, the most appropriate treatment (sequence) depends on patient and disease characteristics. This article summarises the recommendations of a multidisciplinary group of Belgian experts in sequencing treatments for patients with mCRPC, with a focus on radium-223 dichloride.

(BELG J MED ONCOL 2019;13(6): 240–250)

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Adjuvant chemotherapy of colon cancer: 3 versus 6 months

BJMO - volume 13, issue 6, october 2019

C. Debeuckelaere MD, L. Triest MD, T. Vandamme MD, PhD, B. Van den Heuvel MD, K. Papadimitriou MD, PhD, M. Rasschaert MD, PhD, H. Prenen MD, PhD, M. Peeters MD, PhD

Summary

For over a decade, oxaliplatin-based adjuvant chemotherapy has been the gold standard for resected early colon cancer. Oxaliplatin is known to cause polyneuropathy, which affects quality of life dramatically. In recent years, there has not been any progress in the development of novel agents to replace oxaliplatin as adjuvant therapy. Consequently, there is a growing interest to investigate whether a shorter course of chemotherapy is sufficient. This article will discuss the history of adjuvant treatment in early-resected colon cancer, the toxicity of oxaliplatin, the results from the IDEA meta-analysis and future prospects.

(BELG J MED ONCOL 2019;13(6):234–239)

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Interventions in non-metastatic castration-resistant prostate cancer: earlier seems better

BJMO - volume 13, issue 4, june 2019

D. Schrijvers MD, PhD

SUMMARY

Patients with non-metastatic castration-resistant prostate cancer benefit from an early treatment in terms of metastasis-free survival. Three drugs were compared with placebo in large randomised trials (SPARTAN, PROSPER, ARAMIS) and all showed an improvement in median metastasis-free survival. They differ in some of the secondary endpoints and side effects. This article discusses the results and the impact for patients with non-metastatic castration-resistant prostate cancer.

(BELG J MED ONCOL 2019;13(4):129–131)

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Retrospective study of survival and consecutive treatments of patients treated with aflibercept plus FOLFIRI in second line for metastatic colorectal cancer in Belgium

BJMO - volume 13, issue 3, may 2019

A. Bols MD, PhD, K. Geboes MD, M. De Man MD, T. Delaunoit MD, I. Sinapi MD, J. Carrasco MD, PhD, M. Peeters MD, PhD

SUMMARY

A retrospective study in patients treated with aflibercept plus FOLFIRI in second line for metastatic colorectal cancer (mCRC) was conducted in Belgium. A total of 102 patients (64.7% males; 62.9 ± 9.8 [mean ± SD] years-old; 36.3% Eastern Cooperative Oncology Group [ECOG] 0 and 63.7% ECOG 1 status) were included. At the end of the study, 47.1% of patients were deceased and 49% were still alive. The median overall survival (± SD) was 15.7 ±1.2 months (no statistically significant difference [p=0.706; log rank test] in survival as a function of the ECOG status). The median progression-free survival was 7.1 ±1.0 months (no statistically significant difference [p=0.732; log rank test] in progression-free survival as a function of the ECOG status). Aflibercept treatment was still ongoing in 22.5% of the patients. The treatment was stopped in 79 (77.5%) patients. In 16 patients (15.7%), treatment with aflibercept was discontinued due to drug toxicity. The average aflibercept treatment duration was 4.5 ± 4.5 months and the average number of aflibercept administrations was 8.7 ± 6.7. Overall, 62% of the patients having interrupted aflibercept received at least one targeted therapy or one chemotherapy after aflibercept. The three most frequent targeted therapies were regorafenib (46%), panitumumab (30%) and cetuximab (18%). The four most frequent chemotherapies were FOLFIRI (44.7%), FOLFOX (12.8%), irinotecan (12.8%) and capecitabine (12.8%). The results obtained using a retrospective observational real-life setting in Belgium globally corroborate those observed in the VELOUR randomised placebo-controlled trial.

(BELG J MED ONCOL 2019;13(3):98–104)

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

BJMO - volume 13, issue 2, march 2019

A. Awada MD, PhD, J-F. Baurain MD, PhD, P. Clement MD, PhD, P. Hainaut MD, S. Holbrechts MD, PhD, K. Jochmans MD, V. Mathieux MD, J. Mebis MD, M. Strijbos MD, PhD, C. Vulsteke MD, PhD, T. Vanassche MD, P. Verhamme MD

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)

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