N. D’Haene MD, PhD

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

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)

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)

The Belgian next generation sequencing guidelines for haematological and solid tumours

SUMMARY

Targeted next generation sequencing is a complex procedure including the ‘wet bench’ and ‘dry bench’ parts. Both parts are composed of many steps for which optimal assay conditions and settings must be determined.

The aim of these guidelines is to provide generic, platform independent, recommendations for targeted next generation sequencing tests to detect acquired somatic mutations in DNA, in (haemato)-oncology that are complementary to the ISO 15189 norm (medical laboratories) in order to:

1. facilitate the implementation of the required quality metrics for the detection of somatic variants by next generation sequencing in oncology and haemato-oncology in the Belgian laboratories,
2. harmonise test validation and verification,
3. harmonise clinical interpretation and reporting of variants and,
4. assure and maintain optimal test performance by establishing procedures and modalities for internal quality control and external quality assessments.

(BELG J MED ONCOL 2017;11(2):56–67)

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)

Clinical application of targeted next generation sequencing for lung cancer patients

Summary

The successes of targeted agents in patients with molecularly defined tumours and improvements in genomic technology have generated enthusiasm for incorporating genomic profiling into clinical cancer practice and molecular testing has now become a standard of care for lung cancer. International guidelines recommend testing for EGFR mutations and ALK gene rearrangement to guide patient selection for therapy. However, different potentially targetable oncogenes, such as KRAS, PIK3CA, BRAF, ERBB2 or MET, for which agents are being evaluated, have been proposed as valuable for managing patients with lung cancer. Recently, the development of next generation sequencing has enabled simultaneous detection of many clinically relevant mutations in different genes in a single test. In this study, we have evaluated the clinical utility of targeted next generation sequencing, using a 22 genes panel, for patients with lung cancer on 234 samples, including cytology, biopsies and surgical resections, from two different institutions tested in routine daily practice since validation and accreditation of the method (BELAC ISO15189). On the 234 samples tested, only one case could not be sequenced due to an insufficient quantity of available tissue. Among the 233 cases tested, 223 (95.7%) samples were sequenced successfully. The median turnaround time between reception of the sample in the laboratory and report release was one week. The most frequent mutations were found in TP53 (42.1%) and KRAS (35.9%). Of successfully sequenced cases, 137 potentially actionable mutations were identified in 130 patients (58.3%), including 80 KRAS mutations, 26 EGFR mutations, fourteen BRAF mutations, eight PIK3CA mutations, three PTEN mutations, two ERBB2 insertions, two NRAS mutations and two MAP2K1 mutations. Overall, next generation sequencing can be applied in daily practice even for small samples, such as lung biopsies or cell blocks. Moreover, it provides clinically relevant information for lung cancer patients.

(BELG J MED ONCOL 2015;9(7):272–78)

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)