T. Feys MBA, MSc

The changing first-line treatment landscape for patients with ALK-positive NSCLC

The discovery of the EML4-ALK fusion gene in a limited subset of non-small-cell lung cancer (NSCLC) patients and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistance to crizotinib regularly develops ultimately leading to disease progression. Since then, several novel ALK targeting tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, lorlatinib and ensartinib have been developed. While initially showing their worth in the second line treatment of ALK-positive advanced NSCLC, more recent studies have also demonstrated superior efficacy of second-generation ALK inhibitors over crizotinib in the first-line treatment of these patients. As a result, second-generation ALK inhibitors have largely replaced crizotinib as the preferred first-line treatment for patients with advanced ALK-positive NSCLC. In this article we want to provide an overview of the current evidence on the best sequence in the treatment of ALK-positive NSCLC patients.

Overcoming crizotinib resistance in ROS1-positive NSCLC

Rearrangements involving the ROS1 gene are found in approximately 2% of patients with non-small-cell lung cancer (NSCLC). Based on the results of the pivotal PROFILE 1001 trial, the multikinase tyrosine kinase inhibitor (TKI) crizotinib became the first targeted treatment option for patients with advanced ROS1-positive NSCLC in 2016. Unfortunately, responses to crizotinib tend not to be durable and almost all patients eventually develop disease progression after a certain amount of time, often involving brain metastases. To overcome this crizotinib resistance, several next generation ROS1 inhibitors have been developed and tested in the treatment of crizotinib-pretreated and treatment naïve ROS1-positive advanced NSCLC.

Dual EGFR-VEGF strategy in EGFR-mutant NSCLC

The VEGF pathway is well-recognized mediator of angiogenesis and tumorigenesis in many cancer types. As a result, multiple therapeutic agents targeting this pathway have been developed and were subsequently registered in multiple tumor types. Interestingly, preclinical studies have demonstrated a close relationship between VEGF and EGFR pathways. Based on this observation, several studies have investigated whether the addition of a VEGF-targeting agent to an EGFR-directed tyrosine kinase would provide clinical benefit in patients with EGFR-mutant non-small cell lung cancer. In recent years, several large, randomized studies demonstrated that the addition of bevacizumab or ramucirumab to EGFR TKIs substantially improves the progression-free survival (PFS) in this setting. The topline results of these studies will be briefly discussed in this article.

Real-world treatment practices for EGFR-mutant NSCLC patients

The introduction of tyrosine kinase inhibitors (TKIs) targeting mutant epidermal growth factor receptor (EGFR) has revolutionized the treatment of patients with EGFR-mutant advanced NSCLC. In the recently published REVEAL trial, investigators assessed the current clinical practice for these patients in Belgium revealing some striking observations. In fact, one out of five EGFR-mutant advanced NSCLC patients in this study did not receive ESMO standard of care in first line. After progression on a first EGFR-TKI, Moreover, nearly 30% of patients were not tested for the presence of a T790M mutation after progression on first-line treatment with an EGFR TKI and a quarter of patients did not receive subsequent systemic treatment for NSCLC. These findings underscore the need for more diligent decision-making in the treatment of these patients in order to maximize the clinical potential of EGFR TKIs.

New oncology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

Highlights of the 23rd annual meeting of the Belgian Society of Medical Oncology (BSMO)

SUMMARY

As always, the annual meeting of the Belgian Society of Medical Oncology (BSMO) wanted to provide a platform for the dissemination of practice-changing information relevant to Oncology within Belgium. In light of the ongoing global pandemic, the 23^rd annual meeting went virtual in 2021. This did not detract from the engaging line up of presentations, with a particular emphasis on treatment breakthroughs in a variety of cancers. In addition to this, several projects with a local impact on the Belgian Oncology landscape were presented. Get up to date with the 2021 BSMO 23^rd annual meeting with these highlights.

BELG J MED ONCOL 2021;15(3):134-44

Highlights in HER2-positive breast cancer

In the field of Human Epidermal Growth Factor Receptor 2 (HER2) positive early breast cancer, an interesting Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY trial was presented at SABCS 2020. In addition, BluePrint RNA sequencing was used in an attempt to predict the benefit of adjuvant pertuzumab in this trial. Other interesting data in early HER2-positive breast cancer came from the use of neratinib as extended adjuvant therapy. In the metastatic setting, results of the PERTAIN study, the first randomised phase II trial to assess the addition of pertuzumab to trastuzumab and an aromatase inhibitor in the presence or absence of induction chemotherapy, were presented. Finally, a long list of abstracts featured results with novel HER2-directed therapies, including the antibody-drug conjugate trastuzumab deruxtecan, the tyrosine kinase inhibitor tucatinib and the investigational monoclonal antibody margetuximab.