T. Feys MBA, MSc

Long-term data solidify nivolumab + cabozantinib as a standard first line treatment for patients with advanced renal cell carcinoma

Based on the results of several large, randomised phase III studies, combinations of an immune checkpoint inhibitor (ICI) and a tyrosine kinase inhibitor (TKI), or dual ICI therapy were established as the preferred first line treatment for patients with metastatic renal cell carcinoma (mRCC). During the 2024 ASCO GU conference, long-term data of the pivotal CheckMate 9ER study evaluating the combination of cabozantinib (CABO) and nivolumab (NIVO) in previously untreated mRCC patients were presented.¹ After a median follow-up of 55.6 months, CABO-NIVO continued to be associated with a significantly longer progressionfree (PFS) and overall survival (OS), and a significantly higher objective response rate (ORR) than sunitinib alone.¹ As such, these long-term data of the CheckMate 9ER study solidify the combination of CABO-NIVO as a preferred first line treatment choice for patients with mRCC.

Immunotherapy: a new standard first-line treatment for patients with advanced dMMR/MSI-H endometrial cancer

During the last decade, immune checkpoint inhibition (ICI) emerged as an important therapeutic pillar across a broad range of cancer types. Given the high incidence of DNA mismatch repair deficiency (dMMR) in endometrial tumours, this treatment modality has also been studied in the treatment of patients with recurrent or advanced endometrial cancer (EC). These studies have revealed that particularly tumours with dMMR or a high level of microsatellite instability (MSI-H) are sensitive to ICI-based therapies. While ICI monotherapy initially proved its worth in recurrent or advanced dMMR/MSI-H EC patients with failure after platinum-based chemotherapy, more recent studies have successfully evaluated combinations of an ICI and chemotherapy in the first-line treatment of these patients. Based on the results of the ENGOT-en6/RUBY trial, NRG-GY018, AtTEnd and DUO-E studies it is safe to say that ICI-chemotherapy combinations should be the new standard first-line treatment for recurrent or advanced dMMR/MSI-H EC patients. Several studies are currently underway to evaluate ICI monotherapy as first-line treatment for these patients and the results of these trials are eagerly awaited.

Tumour-agnostic therapies in oncology: a big leap towards true treatment personalisation

The advent of precision medicine, led by the discovery of druggable genes and informed by next-generation sequencing, has drastically changed the therapeutic landscape in oncology. These evolutions revealed a spectrum of actionable genetic alterations shared across a broad spectrum of tumour types, which fuelled the hope for cancer drugs that are capable to interfere with these oncogenic pathways irrespective of the organ of origin of the tumour. In recent years, several of these tumour-agnostic drug targets have been approved by regulatory agencies and it is to be expected that more will follow in the years to come. This article briefly explains the rationale for tumour-agnostic approvals followed by an overview of the currently approved and emerging pan-tumour targets. In addition, the paper addresses a new tool that was developed by the European Society of Medical Oncology (ESMO) to assess the tumour-agnostic potential of new drugs (ECTA-S) and inform the clinical development of potentially tumour-agnostic drugs.

Managing CNS metastases in patients with EGFR-mutant non-small-cell lung cancer

ABSTRACT

The central nervous system (CNS) is a dominant place of metastasis in patients with non-small cell lung cancer (NSCLC). The tendency to spread to the CNS is even more pronounced in patients presenting with an oncogenic driver mutation in EGFR. While the first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are associated with a limited intracranial activity, the third generation EGFR TKI osimertinib passes the blood-brain-barrier (BBB) much more effectively, leading to a markedly higher activity in the CNS. Based on the compelling intra- and extracranial activity of osimertinib compared to earlier EGFR TKIs in the pivotal FLAURA trial, this agent has become the standard of care first line treatment for patients with EGFR-mutant NSCLC, including those who present with baseline CNS metastases. More recently, results of the FLAURA2 trial showed that combining osimertinib with chemotherapy in first line results in a more pronounced clinical activity, especially in the CNS. In addition, also the upfront use of local therapy prior to the start of osimertinib is being explored as a way to improve the CNS activity of this agent. Osimertinib does not only target existing brain metastases, it also prevents the development of new brain lesions. This CNS protective effect is now also being leveraged in the adjuvant treatment of patients with earlier stage, EGFR-mutant NSCLC.

Tumour-agnostic therapies in oncology: a big leap towards true treatment personalization

The advent of precision medicine, led by the discovery of druggable genes and informed by next-generation sequencing, has drastically changed the therapeutic landscape in oncology. These evolutions revealed a spectrum of actionable genetic alterations shared across a broad spectrum of tumour types, which fuelled the hope for cancer drugs that are capable to interfere with these oncogenic pathways irrespective of the organ of origin of the tumour. In recent years, several of these tumour-agnostic drug targets have been approved by regulatory agencies and it is to be expected that more will follow in the years to come. This article briefly explains the rationale for tumour-agnostic approvals followed by an overview of the currently approved and emerging pan-tumour targets. In addition, the paper addresses a new tool that was developed by the European Society of Medical Oncology (ESMO) to assess the tumour-agnostic potential of new drugs (ECTA-S) and inform the clinical development of potentially tumour-agnostic drugs.

Abemaciclib: an important weapon in the treatment arsenal for patients with hormone-receptor positive, HER2- breast cancer

New oncology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J MED ONCOL 2024;18(5):221–2)