Tom Feys MBA, MSc

Biomarkers for immune checkpoint inhibition

Summary

Immune checkpoint inhibitors are effective in restoring the T-cell mediated immune response and can achieve a deep and durable response in a small subset of cancer patients. As only 15% to 25% of the patients with advanced NSCLC will benefit from immunotherapy, a predictive biomarker is required to select patients who will potentially respond. To date, the most intensively studied potential biomarkers consist of the programmed death ligand 1 (PD-L1) expression, the tumour mutational burden (TMB) and the tumour micro-environment (TME), each with its own advantages and challenges. This article will briefly describe each of these biomarkers and will touch upon the relationship between certain genetic modifiers and a response to immunotherapy.

First-line immunotherapy for patients with advanced NSCLC: where do we stand?

Summary

Over the last decades we have witnessed substantial progress in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). While several targeted therapies entered the therapeutic arena for patients harbouring oncogenic driver mutations, the treatment for patients with non-oncogene driven NSCLC remained largely chemotherapy based. In recent years however, also the treatment paradigm for these patients underwent a transformation. In fact, convincing data generated by a long list of randomized trials, established immune checkpoint inhibition as a new therapeutic strategy for an ever-growing proportion of NSCLC patients. Within a couple of years immune checkpoint blockade moved from the second line setting to first-line therapy and broadened its scope from advanced to locally advanced NSCLC. As such, it turned the first-line treatment of advanced NSCLC into a competitive battlefield of crucial importance. Currently, three immunotherapeutic strategies have proven their worth in the first line treatment of patients with advanced, non-oncogene driven NSCLC: the use of PD-(L)1 inhibitors in monotherapy, combining PD-(L)1 inhibitors with chemotherapy, and combining PD-(L)1 inhibitors with other immune checkpoint inhibitors (mainly anti CTLA-4). In this article we will review the most recent clinical data generated with these three therapeutic strategies and provide updates on the biomarkers that can guide the choice for one of these options in the individual patient.

What’s new for patients with oncogenedriven non-small-cell lung cancer?

Summary

Over the last decades, the comprehensive molecular characterization of non-small-cell lung cancer (NSCLC) has expanded our understanding of the cellular origins and molecular pathways affected in this lung cancer subtype. Many of these genetic alterations represent potential therapeutic targets for which new drugs are constantly under development. As such, targeted therapy has emerged as the therapeutic cornerstone for patients with oncogene-driven advanced NSCLC. This personalized treatment strategy not only improved the treatment outcomes compared to traditional chemotherapy, it also had a significant impact on the quality of life of patients. Nowadays, targeted agents directed against epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements have become standard therapy for patients harbouring these genetic aberrations. In addition to this, targeted agents directed against other, more rare, genetic aberrations (e.g. ROS1, NTRK, MET, RET, etc.) have generated promising results and several of these agents will enter the NSCLC treatment arsenal in the near future. This article provides an overview of key studies in patients with oncogene-driven NSCLC that were presented in the past year.

Journal Scan

SUMMARY

The goal of this new section in the BJMO is to provide a snapshot of pivotal studies published in recent issues of the most important international journals focusing on oncology. Importantly, the selection of the studies discussed here is the sole responsibility of the publisher and was not influenced by third parties. Do you miss an important study, or did you read a hidden jewel that deserves to be shared with your colleagues? Please let us know (editor@bjmo.be) and we will make sure to include it in the journal scan section of the next BJMO issue.

(BELG J MED ONCOL 2020;14(2):80–3)

Immuno-oncology combinations: rationale and clinical implications in melanoma, renal cell carcinoma and lung cancer

ABSTRACT

Over the past years, immune checkpoint inhibitors have been widely used for the treatment of a broad range of malignancies. Unfortunately, only a proportion of patients derives long-term benefit from these therapeutics. In fact, a majority of patients fails to respond to immune checkpoint inhibition, while others relapse after a certain time. In an attempt to increase the response rate of tumours to these drugs, investigators have looked into the potential of combining different immunotherapeutic agents. Since inhibitors of the immune checkpoints CTLA-4 and PD-(L)1 have different modes of action and given the fact that blocking one of both pathways results in an upregulation of the other, provide a theoretical rationale to combine these agents. This review provides an overview of clinical studies evaluating combinations of CTLA-4 and PD-(L)1 inhibitors in the treatment of melanoma, renal cell carcinoma and non-small-cell lung cancer.

The 13^th Belgian symposium on the integration of molecular biology advances into oncology clinical practice (BSMO/Bordet meeting)

SUMMARY

On the 22^nd and 23^rd of November 2019, the Jules Bordet Institute and the Belgian Society of Medical Oncology (BSMO) hosted the 13^th Belgian symposium on the integration of molecular biology advances into oncology clinical practice. In the course of the symposium, a fine selection of Belgian and international key opinion leaders discussed the clinical impact of molecular biology advances in a plethora of cancer types.

(BELG J MED ONCOL 2020;14(1):31–41)

Highlights in melanoma

The introduction of immune checkpoint inhibitors highly impacted the treatment landscape of melanoma over the last decade. At ESMO 2019, several abstracts again proved the clinical potential of these agents in the treatment of melanoma, both in (neo)adjuvant as in the advanced setting. In addition to this, promising results were presented with talimogene laherparepvec in early and in metastatic melanoma. Finally, several abstracts also discussed combinations of targeted agents and immunotherapy in patients with advanced melanoma.