Articles

PIK3CA in breast cancer: a Belgian practical testing guideline

BJMO - volume 15, issue 6, october 2021

G. Broeckx MD, Ir A. Hébrant PhD, N. D’Haene MD, PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, I. Vanden Bempt PhD, P. Aftimos MD, P. Neven MD, PhD, P. Pauwels MD, PhD

SUMMARY

The PI3K/AKT pathway plays an important role in the oncogenesis of breast cancer. Activating mutations in PI3K, more specifically in the p110α catalytic unit of the class IA PI3K isoform (encoded by the PIK3CA gene), lead to an increased conversion of phosphatidylinositol-4,5-biphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3) inducing a cell signalling cascade for cell proliferation and cell survival. PIK3CA mutations are found in 20–32% of all breast cancers (BC), particularly in hormone sensitive (HR+) BC. In breast cancer, activation of the PI3K pathway coexists with the activation of the oestrogen receptor pathway. Inhibition of one of these pathways may lead to compensatory activation of the other pathway. Therefore, mono-therapy with PI3K inhibitors has limited activity in HR+ BC. On the other hand, this explains the efficacy of a PI3K/ER dual blockade. This dual blockade is researched in the phase III SOLAR-1 trial. In the PIK3CA-mutated cohort of this study, there is an improved outcome for patients with advanced or metastatic HR+ HER2- BC, harbouring activating hotspot mutations in PIK3CA and previously treated with an aromatase inhibitor and no more than one line of endocrine therapy for MBC, who received fulvestrant (a selective oestrogen receptor degrader) and alpelisib (a p110α-isoform specific inhibitor) in comparison to the patients that received fulvestrant and placebo. Based on these results, a medical need program for alpelisib in a heavily pre-treated setting and an amendment were approved by the EMA and the Belgian FAMHP. Supporting this data, we propose the mutational analysis of PIK3CA, preferably by next generation sequencing on FFPE tumour material, in advanced or metastatic HR+ HER2- BC, previously treated with three lines of systemic therapy.

(BELG J MED ONCOL 2021;15(6):304-14)

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Genetic and molecular biology in pancreatobiliary cancers: Testing for pancreatobiliary cancer in the context of the Belgian NGS convention

BJMO - volume 15, issue 4, june 2021

Ir A. Hébrant PhD, H. Antoine-Poirel MD, PhD, K.B.M. Claes PhD, F. Dedeurwaerdere MD, J. Van der Meulen MD, F. Lambert MD, J. Van Huysse MD, G. Martens MD, PhD, N. D’Haene MD, PhD, K. Geboes MD, PhD, P. Pauwels MD, PhD, A. Jouret-Mourin MD, PhD, P. Peeters MD, M. van den Eynde MD, PhD, R. Salgado MD, PhD, P-J. Van Dam MD, P. Lefesvre MD, PhD, X. Sagaert MD, S. Metsu PhD, A. Demols MD, PhD, J-L. van Laethem MD, PhD

SUMMARY

Pancreatobiliary cancers (PBC) group pancreatic and biliary tract cancers and are among the cancers with the lowest survival rate. Emerging data suggest that novel biomarker-specific targeted therapies can be proposed for selected populations with survival benefit. This review summarises the scientific evidence to test for these biomarkers in order to optimise the management of pancreatobiliary cancers, within the context of the Belgian NGS convention.

(BELG J MED ONCOL 2021;15(4):170-6)

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Guidelines for the detection of NTRK fusions. A report from the Belgian Molecular Pathology Working Group

BJMO - volume 15, issue 3, may 2021

P. Pauwels MD, PhD, G. Broeckx MD, F. Dedeurwaerdere MD, C. Galant MD, Ir A. Hébrant PhD, I. Vanden Bempt PhD, K. Van de Vijver MD, PhD, J. Van Huysse MD, B. Weynand MD, PhD, N. D’Haene MD, PhD

(BELG J MED ONCOL 2021;15(3):112-6)

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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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Molecular test algorithms for digestive tumours

BJMO - volume 13, issue 1, february 2019

Ir A. Hébrant PhD, Ir , A. Jouret-Mourin MD, PhD, G. Froyen PhD, J. Van der Meulen MD, M. De Man MD, R. Salgado MD, PhD, M. van den Eynde MD, PhD, N. D’Haene MD, PhD, G. Martens MD, PhD, E. van Cutsem MD, PhD, H.A. Poirel MD, PhD, S. Tejpar MD, PhD, J-L. van Laethem MD, PhD, K. Geboes MD, PhD, P. Pauwels MD, PhD, F. Dedeurwaerdere MD, B. Maes MD, PhD, J. De Grève MD, PhD, J. Vanhuysse , P. Peeters MD, L. Vanacker MD, M. Gomez-Galdon , M. Chintinne MD, PhD, A. Hendlisz MD, PhD, G. de Hertogh MD, X. Sagaert MD, M. Peeters MD, PhD, P. Vannuffel , P. Lefesvre MD, PhD, J. Vermeij , M. Simoens , T. Van den Mooter MD, N. van Damme , M. Van den Bulcke PhD

The Belgian Commission of Personalized Medicine has been created to advise the federal government on all matters related to personalised medicine in oncology, including the reimbursement of molecular tests. Here, we propose the Belgian strategy for molecular testing in the digestive tumours within a scientific-based framework. For each tested biomarker, a clinical test level is attached, which is key to establish the relevance of the test and to define the reimbursement. For each digestive tumour type, the different molecular tests are represented as decision trees with its test utility, test level and a brief technical test description.

(BELG J MED ONCOL 2019;13(1):4–10)

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PD-L1 Testing for Non-Small Cell Lung Cancer: Belgian Guidelines

BJMO - volume 12, issue 5, september 2018

P. Pauwels MD, PhD, M. Remmelink MD, PhD, D. Hoton MD, J. van Dorpe MD, PhD, K. Dhaene MD, PhD, F. Dome MD, A. Jouret-Mourin MD, PhD, B. Weynand MD, PhD, N. D’Haene MD, PhD

In recent years, the outcome of patients with non-small cell lung cancer (NSCLC) has improved thanks to the development of targeted therapies. Currently, the introduction of immunotherapy for lung cancer patients offers new treatment opportunities. The pathologist is now asked to provide the most accurate possible diagnosis in association with theranostic information in order to provide the best therapeutic option. For immunotherapy, programmed death receptor ligand 1 (PD-L1) status is, at the present, the required biomarker for patient stratification, at least in first line treatment. Different international societies have already underlined the importance of guidelines for managing samples of non-small cell lung cancer NSCLC. With the goal of adapting these international recommendations to the Belgian landscape, Belgian guidelines were published in 2016. This update integrates immunotherapy into the previously published guidelines.

(BELG J MED ONCOL 2018;12(5):233–238)

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Second-line treatment of non-small cell lung cancer adenocarcinoma patients not harbouring an oncogene driver mutation anno 2017–2018: A consensus group meeting

BJMO - volume 12, issue 2, march 2018

P-E. Baugnée , L. Bosquée MD, PhD, C. Compère MD, N. D’Haene MD, PhD, I. Demedts , D. Galdermans MD, P. Germonpré , M. Gustin , V. Ninane MD, PhD, S. Ocak , P. Pauwels MD, PhD, T. Pieters MD, PhD, A. Sadowska MD, A. Sibille MD, V. Surmont MD, PhD, J. Vansteenkiste MD, PhD

Summary

The treatment landscape for patients with advanced non-small cell lung cancer, who do not harbour an oncogenic driver abnormality, has changed dramatically over the last years. Second-generation antiangiogenic agents, such as nintedanib and ramucirumab, and particularly PD-1/PD-L1 inhibitors, such as nivolumab, pembrolizumab and atezolizumab have shown to prolong survival in pretreated non-small cell lung cancer patients. Immune checkpoint inhibition in the treatment of advanced non-small cell lung cancer comes with the promise of durable responses in responding patients. Nevertheless, one must appreciate that the average response rate seen with these PD-1/PD-L1 targeting agents is only about 20%. While PD-L1 testing may be used as an enrichment biomarker, a substantial proportion of patients still do not benefit from these agents. They could benefit from alternative therapeutic options, including novel anti-angiogenic agents. In this paper, a treatment algorithm is proposed that aims to optimise the second-line treatment choice for patients with lung adenocarcinoma, based on the available clinical data.

(BELG J MED ONCOL 2018;12(2):61–66)

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