J. Blokken PhD, PharmD

Central nervous system metastases in melanoma: still an issue

Melanoma is the third cause of central nervous system (CNS) metastases and roughly 40–50% of advanced melanoma patients will develop CNS metastases. Importantly, the incidence of brain metastases may rise even further as systemic treatment of stage IV melanoma improves. In addition, CNS metastases are more frequent in BRAF-mutated melanoma. Finally, as responses in intracranial vs. extracranial sites may be heterogeneous, the efficacy of systemic therapy on brain metastases may be difficult to predict.^1–4 Although the clinical survival outcomes of melanoma patients with brain metastases have been significantly improved due to major advances in systemic therapy, there still remain to be many challenges.

Highlights in melanoma

The 2023 annual European Association of Dermato-Oncology (EADO) congress featured exciting developments in melanoma research. In the adjuvant setting, discussions centred around new biomarkers for treatment response, the role of radiotherapy and new approaches in immunotherapy. Interesting updates were also presented for the treatment of metastatic melanoma, including triple combinations of BRAF plus MEK inhibitors (BRAFi/MEKi) with immune checkpoint inhibitors (ICIs), an IDO/PD-L1-targeting peptide vaccine with nivolumab, and AS01B with myeloid dendritic cells and ICIs.

Journal Scan

In this section of the BJMO, we aim 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 2023;17(4):135–8)

Antibody-drug conjugates in lung cancer: a paradigm shift on the horizon?

Antibody-drug conjugates (ADCs) are a unique class of drugs that combine the power of cytotoxic chemotherapy with that of targeted therapy to deliver highly potent cytotoxic agents to cancer cells that express a pre-defined cell surface target. In 2020, trastuzumab deruxtecan became the first FDA-approved ADC for the treatment of non-small cell lung cancer (NSCLC). Since then, two other ADCs have been granted an FDA Breakthrough Therapy Designation in this setting: patritumab deruxtecan and telisotuzumab vedotin. So far none of these ADCs received EMA-approval for the treatment of lung cancer yet. Nonetheless, several early-phase trials are assessing various novel ADCs in patients with advanced lung cancer and have demonstrated promising efficacy. This review provides an overview of the structure and relevant clinical data of ADCs currently under investigation for the treatment of advanced lung cancer.

Targeted therapy and immunotherapy in early-stage non-small cell lung cancer

For many years, the treatment options for patients with early-stage non-small cell lung cancer (NSCLC) were limited to surgery, with or without chemotherapy. When chemotherapy was used, a platinum-based doublet regimen has been the long-standing standard adjuvant treatment for resected patients with stage II-III disease. Adjuvant chemotherapy results in a benefit of disease-free survival (DFS) and overall survival (OS) in early-stage NSCLC with an absolute survival benefit of 4-5% compared to observation or best supportive care. In recent years, however, early-stage NSCLC has been entering the era of precision medicine. Recent trials have been testing the efficacy both of driver mutation-specific tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) (Figure 1). For oncogene-addicted disease, clinical trials mostly focused on Epidermal Growth Factor Receptor mutations (EGFRm) and Anaplastic Lymphoma Kinase (ALK) rearrangements. In the immunotherapy trials, many pharmacological agents have been tested in the adjuvant as well as neoadjuvant setting.¹ In this review, we aim to report on the already available literature data with targeted agents and immunotherapy in early-stage NSCLC, focusing on the most practice-changing results and new perspectives.

Immunotherapy: a game changer for patients with extensive stage small cell lung cancer

Over the past years, immune checkpoint inhibition has caused a dramatic therapeutic shift in the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). After more than three decades without meaningful improvements in the treatment paradigm for these patients, combinations of platinum-etoposide with either durvalumab, or atezolizumab finally resulted in improved survival outcomes. Notwithstanding the convincing results with these innovative regimens in their respective clinical trials, real-world data on the safety and efficacy of chemo-immunotherapy in patients with ES-SCLC are still relatively scarce. Reassuringly, however, all the available data continue to point towards a clinical benefit of PD-L1 inhibitors in combination with platinum-etoposide vs. chemotherapy alone in this setting. Importantly, this benefit was also observed in patients who would not have been eligible for the pivotal clinical trials evaluating these regimens, including patients with a poor performance status.

Journal Scan

In this section of the BJMO, we aim 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 2023;17(3):100–3)