P. Pauwels MD, PhD

Therapy-orienting testing of EGFR inhibitor-resistant non-small cell lung cancer

SUMMARY

Somatic sensitising mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are detected in approximately 10% of patients with advanced non-squamous non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment option for patients with an actionable EGFR mutation. Despite initial responses, the majority of patients progress within one to two years after EGFR-TKIs treatment initiation.

The most common mechanism of resistance is the development of an additional EGFR-T790M mutation in exon 20, found in 50–60% of EGFR-mutant NSCLC patients who were rebiopsied on EGFR-TKI treatment. Phase II and III trials with osimertinib, a third-generation EGFR-TKI, demonstrated an objective response rate (ORR) of 60–70% and median progression-free survival (mPFS) of 10–11 months in EGFR-T790M-positive tumours.

A tissue biopsy of a progressing lesion for confirmation of histology and molecular characterisation is a critical consideration. However, a repeat tissue biopsy is not possible for every patient. Therefore, a liquid biopsy can be considered for EGFR-T790M mutation testing. Indeed, clinical trials testing osimertinib have shown similar clinical outcomes (ORR and mPFS on osimertinib) in patients with T790M-positive plasma versus T790M-positive tumour tissue.

Osimertinib clearly expands relapse treatment options for advanced stage EGFR-mutant NSCLC. Testing for EGFR-T790M at acquired resistance should become a standard component of patient care in EGFR-mutant tumours. In this manuscript, we propose and discuss two possible clinical diagnostic algorithms that could be used for the therapy-orienting testing of EGFR-TKI-resistant NSCLC patients. Tissue and liquid biopsies involve challenges in terms of specific clinical role, safety, logistics, and cost.

(BELG J MED ONCOL 2017;11(5):226–233)

Pathological diagnosis and molecular testing in non-small cell lung cancer: Belgian guidelines

Summary

In recent years, the management of patients with non-small cell lung cancer has been modified thanks to the development of targeted therapies. The pathologist is now asked to give the most accurate possible diagnosis in association with theranostic information in order to provide the best therapeutic option.
Different international societies have already underlined the importance of guidelines for managing samples of non-small cell lung cancer. These Belgian guidelines have the goal of adapting these international recommendations to the Belgian landscape.

(BELG J MED ONCOL 2016;10(4):123–131)

RAS-testing in colorectal cancer: Belgian guidelines

There is an urgent need for predictive biomarkers in several cancers. In colorectal cancers, KRAS exon 2 mutation analyses were mandatory when considering anti-epidermal growth factor antibody therapy with agents such as cetuximab or panitumumab. However, since the introduction of this testing, a cohort of patients still did not appear to benefit from this therapy. Recently, additional testing for KRAS exon 3 and 4, and NRAS considerably improved the predictive power for therapy success. Therefore, an update of the Belgian guidelines for RAS testing was urgently needed.

(BELG J MED ONCOL 2015;9(5):183–90)

Stratified Medicine: a call for action

(BELG J MED ONCOL 2013;7:15–19)

Tumour markers in metastatic colorectal cancer: clinical implications for treatment with targeted therapy

Targeted therapy with bevacuzimab, cetuximab and panitumumab has expanded the treatment options in metastatic colorectal cancer. Predictive tumour markers for treatment with targeted therapy that have been suggested are Epithelial Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR) expression, KRAS mutation and BRAF mutation status, loss of PTEN and PIK3CA mutation status. Of these, only KRAS has made it into clinical practice. KRAS mutation is a negative predictor for response to cetuximab EGFR inhibitors. No predictive tumour marker for bevacizumab has been identified. In this review, the current evidence on KRAS, BRAF, PTEN, PIK3CA, EGFR and VEGFR expression as predictive tumour markers for targeted therapy is reviewed. (BELG J MED ONCOL 2012;6:52–57)