BJMO - 2022, issue Special, may 2022
T. Feys MBA, MSc
Small cell lung cancer (SCLC) is an aggressive malignancy accounting for 15% of all diagnosed cases of lung cancer. For almost two decades there have been no clinically relevant therapeutic advances for this disease. In recent years, however, extensive-stage (ES) SCLC has become the second thoracic malignancy in which immune checkpoint inhibition (ICI) has caused a dramatic therapeutic shift. Today, combinations of platinumetoposide chemotherapy with durvalumab or atezolizumab are considered standard of care in the first line treatment of patients with ES-SCLC. This article will summarize the clinical basis for this paradigm shift and will discuss some clinical challenges that remain with ICI in the treatment of ES-SCLC.
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BJMO - 2022, issue Special, may 2022
T. Feys MBA, MSc
Over the last decade, the introduction of specific antibodies directed against the programmed death (PD-1) receptor, its ligand PD-L1 (programmed death ligand-1), and the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) receptor into the therapeutic armamentarium for patients with metastatic non-small-cell lung cancer (mNSCLC) led to unprecedented improvements in the survival of a proportion of patients.1 While these immune checkpoint inhibitors (ICIs) were initially evaluated as monotherapy in the second-line setting, more recent clinical trial data have moved these agents to the first-line setting, either as monotherapy or in combination regimens. In fact, it is fair to say that nearly all patients with non-oncogene driven mNSCLC nowadays receive an anti PD-(L)1 based treatment in first line. This article will briefly summarize the available clinical trial data with this therapeutic strategy after which the challenge of choosing the best immunotherapeutic option for the individual patient will be addressed.
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BJMO - 2022, issue Special, may 2022
T. Feys MBA, MSc
The increased use of next generation sequencing has allowed for a detailed interrogation of the molecular landscape of non-small cell lung cancer (NSCLC), identifying different patient subgroups with therapeutically targetable genetic alterations. In this respect, BRAF-mutant NSCLC represent a small, but non-negligible subgroup of NSCLC patients. Data from a pivotal phase II trial have demonstrated that dual BRAF (dabrafenib) and MEK (trametinib) inhibition has durable antitumor activity in patients with a BRAFV600E mutation, making screening for this specific BRAF alteration a mandatory requirement in the diagnostic work-up of metastatic NSCLC. Unfortunately, however, V600E mutations make up only half of all BRAF mutations in NSCLC and the non-V600 patients currently remain orphan of targeted approaches. This article will provide an overview of the clinical trial data obtained with BRAF inhibitors in BRAF-mutant NSCLC after which some of the remaining clinical challenges will be addressed.
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BJMO - 2022, issue Special, may 2022
T. Feys MBA, MSc
MET exon 14 skipping mutation (MET∆ex14) is present in about 3% of non-small cell lung cancers (NSCLCs). Recently, two MET-tyrosine kinase inhibitors (capmatinib and tepotinib) demonstrated their clinical potential in the treatment of this subgroup of NSCLC patients resulting in their FDA approval (EMA approval pending). In their respective pivotal trials, these agents have yielded a promising median progression-free survival (PFS) of 8-12 months. Unfortunately, however, it has also been reported that a third to half of patients show inherent resistance to MET-TKIs. Furthermore, the emergence of acquired resistance to MET-TKIs is inevitable. This article will summarize the clinical trial data generated with capmatinib and tepotinib in this setting after which some insights into the inherent and acquired resistance mechanisms to MET-TKIs will be addressed.
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BJMO - 2022, issue Special, may 2022
T. Feys MBA, MSc
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) dramatically changed the therapeutic algorithm for patients with advanced non-small cell lung cancer (NSCLC). Pivotal trials investigating ICIs in advanced NSCLC have usually excluded patients with oncogenic drivers, hence the outcome of these agents in this population is poorly characterized. The available data are scarce but point towards limited efficacy of ICI in NSCLC patients harboring oncogenic driver mutations. As such, the evidence to date supports the exhaustion of all TKI options prior to immunotherapy or chemotherapy in oncogene addicted tumors.
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BJMO - 2022, issue Special, may 2022
A. Enguita PhD, T. Feys MBA, MSc
In recent years, researchers have evaluated the integration of immunotherapy in the perioperative management of patients with muscle invasive bladder cancer (MIBC), with mixed results. During BMUC 2022, Professor Richard Cathomas (Division of Oncolgy, Cantonal Hospital Graubünden, Switzerland, and University of Zurich, Switzerland) provided an overview of these advances.
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BJMO - 2022, issue Special, may 2022
J. Blokken PhD, PharmD, T. Feys MBA, MSc
Over the past years, next-generation imaging such as multiparametric whole body MRI and PSMA-PET/CT scans have been gaining momentum. Nonetheless, Prof. Padhani argues not to throw bone scintigraphy and CT scans (BS/ CT scans) out just yet. On the contrary, he puts BS/CT scans at the centre of patient care in men with locally advanced prostate cancer (LAPC). However, BS/ CT also comes with important limitations for which next-generation imaging (NGI) can serve as a problem solver after BS/CT scan assessments. During his talk at the BMUC 2022 meeting, Prof. Padhani emphasized the proven prognostic role of BS/CT scans, their predictive role in directing pelvic radiotherapy and for oncologic drug development. Finally, he argued that higher-quality evidence on the management and/or outcomes is needed before BS/CT scans can be substituted by NGI.1
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