T. Feys MBA, MSc

Highlights in breast cancer

SUMMARY

ASCO 2022 featured a couple of breast cancer-related presentations with the potential to shake up the clinical practice. First and foremost, results of the DESTINY-Breast 04 study demonstrated a significant progression-free (PFS) and overall survival (OS) benefit with trastuzumab deruxtecan in the treatment of HER2-low metastatic breast cancer (mBC) patients who received 1–2 prior lines of therapy. By effectively creating a new category of breast cancer, this trial will redefine the classical breast cancer classification and will significantly expand the population of patients who can benefit from HER2-targeted therapy. In TROpICS-02, sacituzumab govitecan, an antibody-drug conjugate directed against TROP-2, was found to delay the disease progression of patients with heavily pre-treated HR+/HER2- advanced breast cancer. Also in HR+/HER2- advanced breast cancer, the MAINTAIN study demonstrated a significant PFS benefit with the continued use of a CDK4/6 inhibitor with a switch in endocrine therapy partner in women who progressed while being treated with a CDK4/6 inhibitor. Finally, ASCO 2022 also showed that the significant PFS benefit obtained from adding the CDK4/6 inhibitor palbociclib to letrozole in the first-line treatment of postmenopausal women with HR+ advanced breast cancer did not translate into a significant OS benefit.

(Belg J Med Oncol 2022;16(5):251–6)

New oncology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J MED ONCOL 2022;16(5):257)

New oncology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J MED ONCOL 2022;16(4):209)

Immunotherapy as a new standard of care first line treatment for patients with extensive stage small-cell lung cancer

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.

First-line immunotherapy for advanced non-small cell lung cancer: available data and clinical challenges

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.

Targeting BRAF-mutations in non-small cell lung cancer: state of the art and future perspectives

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 BRAFV^600E 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.

Targeting MET exon 14 skipping mutations in non-small cell lung cancer

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.