BJMO - 2021, issue BJMO IO Special, december 2021
T. Feys MBA, MSc
Immune checkpoint inhibition (ICI) marked the start of a new era in the treatment of advanced non-small cell lung cancer (NSCLC), inducing a durable response in a substantial proportion of patients. The success of ICI in the advanced setting spurred interest to also examine the potential of this treatment modality in patients with early-stage NSCLC. The first success story in this respect came from the phase III PACIFIC trial, establishing consolidation therapy with durvalumab after chemoradiation as the new standard of care for patients with inoperable, locally advanced NSCLC. More recently, ICI also yielded promising results in patients with resectable NSCLC. In fact, the IMpower010 trial showed that adjuvant atezolizumab after 4-cycles of platinumbased chemotherapy significantly improves the disease-free survival (DFS) compared to best supportive care in patients with stage II-IIIA NSCLC. In addition to this, other studies suggest that neoadjuvant treatment with ICI might result in substantial major pathologic response and pathologic complete response rates, and high rates of R0 resection without a significant delay in the time to surgery.
Read moreBJMO - 2021, issue BJMO IO Special, december 2021
T. Feys MBA, MSc
Malignant pleural mesothelioma (MPM) is a thoracic malignancy that is characterized by a very dismal prognosis. Patients with MPM face a large unmet medical need, with almost no therapeutic advances over the last decade. Recently, however, an important step was made in the management of these patients with the registration of immune checkpoint inhibition (ICI) as a new treatment option for treatment-naïve patients with unresectable MPM. Here we summarize the available evidence supporting the use of ICI in MPM. In addition, the article will address remaining issues such as treatment sequencing and optimal first-line treatment selection.
Read moreBJMO - 2021, issue BJMO IO Special, december 2021
T. Feys MBA, MSc, T. Van Meerhaeghe MD
Over the last years, immune checkpoint inhibition (ICI) emerged as an important therapeutic modality across a variety of cancer types. However, kidney and other solid organ transplant recipients (SOTR) have systematically been excluded from those trials, mainly due to concerns for organ rejection and the use of immunosuppressive therapy in these patients. As a result, little is known about the safety and efficacy of ICI in this setting. Given the increased cancer risk in kidney transplant recipients, with an overrepresentation of certain cancer types for which ICI has become the new standard of care, this represents an important data gap. Based on the scanty data available in the literature, one can conclude that the tumoral response rate to ICI among SOTR suffering from cancer is in line with what is seen in the general cancer population. However, this comes at the cost of an increased risk of allograft rejection and graft loss. This article will briefly discuss the increased cancer risk among kidney transplant recipients after which the available data on the use of ICIs in kidney transplant recipients (KTR) will be summarized, with a particular focus on treatment efficacy and risk factors associated with allograft rejection.
Read moreBJMO - 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).
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