BJMO - 2021, issue BJMO IO Special, december 2021
J. Blokken PhD, PharmD, T. Feys MBA, MSc
Over the last decade, immunotherapy has become increasingly important as a treatment modality for various solid tumors. Unfortunately, the development of immunotherapy in the treatment of gastro-oesophageal malignancies has been lagging behind. More recently, however, impressive advancements have been made with immune checkpoint inhibitors in gastro-oesophageal cancers, with a long list of clinical trials yielding promising, and potentially practice changing results. This review provides an overview of the topline results of these studies.
Read moreBJMO - 2021, issue BJMO IO Special, december 2021
T. Feys MBA, MSc
Over the last decade, immune checkpoint inhibition (ICI) dramatically impacted the treatment of cancer, achieving unprecedented improvements in overall and progression-free survival across a range of advanced and metastatic tumor types. However, despite the impressive efficacy of this treatment modality, the clinical benefit and potential for a long-term response to ICI is restricted to only a subgroup of patients. In this respect, reliable biomarkers that can predict clinical responses to immunotherapy are urgently needed. In recent years, evidence is emerging suggesting that the gut microbiome can modify the efficacy and toxicity of ICI. This article will briefly review the complex interface between the microbiome and the immune system and its effects on ICI, and explore the potential of manipulating the gut microbiome in an attempt to improve the efficacy and safety of ICI.
Read moreBJMO - 2021, issue Special, november 2021
T. Feys MBA, MSc
The discovery of druggable mutations in non-small cell lung cancer (NSCLC) has revolutionised the treatment of these patients. A prime example of this consists of targeting the constitutively activated ROS1 kinase in patients harbouring a genetic ROS1 rearrangement. In 2016, the multikinase tyrosine kinase inhibitor (TKI) crizotinib became the first targeted treatment option for patients with advanced ROS1-positive NSCLC. Unfortunately, however, crizotinib comes with some important drawbacks. First of all, the reduced central nervous system (CNS) penetration of crizotinib makes it unsuitable for patients with metastases in the CNS, a very common finding in ROS1-rearranged NSCLC. This lack of intracranial activity also leads to an increased risk for the development of new CNS lesions. In addition to this, acquired mutations in ROS1 often render patients who initially have a good response, resistant to crizotinib. To address these issue, several new highly potent and CNS penetrant ROS1 inhibitors have been developed (i.e. entrectinib, lorlatinib, repotrectinib), with several studies highlighting their potential as a frontline treatment for patients with advanced ROS1-rearranged NSCLC. Recently, entrectinib became the first of these next-generation ROS1 inhibitors to receive approval by the European Commission for the treatment of ROS1-rearranged advanced NSCLC patients who did not yet receive a ROS1 targeting agent.
Read moreBJMO - 2021, issue Special, november 2021
T. Feys MBA, MSc
Despite the fact that substantial survival improvements were achieved over the last two decades, prostate cancer remains lethal at the metastatic castration-resistant stage (mCRPC) and new therapeutic approaches are needed. The genomic landscape of metastatic prostate cancer reveals that up to 20% of patients harbour somatic mutations in genes involved in DNA damage response pathways, forming the rationale to assess PARP inhibition as a therapeutic modality in this setting. Several clinical trials have demonstrated the potential of PARP inhibition in mCRPC harbouring homologous recombination repair (HRR)-related gene mutations. Recently, these efforts culminated in the EMA approval of olaparib for the treatment of adult patients with mCRPC harbouring a BRCA1/2-mutation who progressed following prior therapy, including a novel hormonal agent (i.e. abiraterone acetate or enzalutamide).
Read moreBJMO - 2021, issue Special, november 2021
J. Blokken PhD, PharmD, T. Feys MBA, MSc
Over the past decade, researchers have tried to tackle RET-driven cancers with various multikinase inhibitors. However, their efficacy was only modest and came at the cost of significant toxicities, leading to high rates of treatment discontinuation. Therefore, the development of RET-specific inhibitors has become paramount. Recently, the highly selective RET tyrosine kinase inhibitors selpercatinib and pralsetinib have demonstrated high response rates in patients with RET-altered non-small cell lung cancer (NSCLC) and thyroid cancer. As brain metastases eventually occur in approximately 50% of patients with RET fusion-positive NSCLC, special attention should go to the intracranial activity of these drugs.
Read moreBJMO - 2021, issue Special, november 2021
T. Feys MBA, MSc, J. Blokken PhD, PharmD
Over the last decade, the introduction of immune checkpoint inhibitors and targeted agents inhibiting BRAF, and MEK signal transduction pathways revolutionised the treatment paradigm for patients with metastatic melanoma. However, to date there is still no consensus on the optimal treatment sequence in BRAF-mutant metastatic melanoma. In the absence of prospective, randomised data, the treatment choice in clinical practice is mainly driven by patient characteristics. More recently, clinical trials are assessing the optimal treatment sequence of targeted therapy and immunotherapy, while other studies are looking into the potential of combining both treatment modalities in first-line.
Read moreBJMO - 2021, issue Special, november 2021
J. Blokken PhD, PharmD, T. Feys MBA, MSc
Approximately 25% of patients with non-small cell lung cancer (NSCLC) are being diagnosed in an early stage of the disease. Even though these patients are eligible for radical surgery, the five-year survival rates for fully resected early-stage NSCLC remains disappointing. In fact, for patients who receive adjuvant chemotherapy after surgery, recurrence rates are high, with approximately half of patients suffering from disease relapse. The design of molecularly oriented studies and the availability of novel potent and less toxic targeted agents paved the way for the evaluation of these drugs in the (neo)adjuvant setting for patients with early-stage NSCLC harbouring oncogenic driver mutations. Here we summarise the results obtained with EGFR-targeted drugs in early-stage NSCLC.
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