T. Feys MBA, MSc

Highlights in lung cancer

The 2022 annual ESMO meeting again featured a long list of interesting lung cancer-related abstracts, ranging from long-term updates of pivotal studies to preliminary data of studies assessing novel treatment strategies for lung cancer. This article will give an overview of the key highlights in lung cancer presented during this meeting. We are grateful to Prof. Lore Decoster, from the University Hospital Brussels, for helping us I selecting the abstracts for this overview and for providing her expert opinion on the different studies.

(Belg J Med Oncol 2022;16(8):395–403)

New oncology reimbursements in Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J MED ONCOL 2022;16(8):421)

Immunotherapy for non-metastatic non-small-cell lung cancer: available data and future perspectives

Over the last decade, immune checkpoint inhibition (ICI) has dramatically changed the treatment landscape for patients with metastatic non-small-cell lung cancer (NSCLC). The success of ICI-based therapy in the metastatic setting fed the interest to also evaluate the potential of immunotherapy in earlier NSCLC disease stages. This article will provide a brief overview of the available, practice-changing data with ICI-based therapy in the neoadjuvant and adjuvant treatment for patients with early-stage NSCLC. Recently, these data led to the EMA approval of atezolizumab as monotherapy in the adjuvant treatment of selected early-stage NSCLC patients. In addition, EMA approval is currently also being sought for the combination of nivolumab and chemotherapy as neoadjuvant therapy for patients with resectable NSCLC. In addition to the results in the (neo)adjuvant setting, this article will also address the clinical basis for ICI-based therapy in unresectable,locally-advanced NSCLC.

The evolving role of immunotherapy in the treatment paradigm for patients with small-cell lung cancer

Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases and is characterized by an aggressive disease course and a particularly poor prognosis. For decades, the best available systemic therapy for patients with extensive-stage (ES) SCLC consisted of platinum-etoposide chemotherapy. In recent years, however, extensive-stage (ES) SCLC has become the second thoracic malignancy in which immune checkpoint inhibition (ICI) proved to prolong the survival of patients. In fact, the phase III CASPIAN and IMpower133 studies showed that the addition of respectively durvalumab and atezolizumab to chemotherapy significantly prolongs the overall survival (OS) of patients with ES-SCLC. The results of these studies quickly established chemo-immunotherapy as the preferred initial treatment for these patients. Nevertheless, the benefit provided by ICI remains to be limited to a proportion of patients and most patients eventually relapse. Therefore, innovative treatment strategies and ICI-based combinations are currently under investigation to further improve the prognosis of patients with ES-SCLC. In addition, studies are looking into the potential of ICI in patients with limited stage (LS) disease.

Immune checkpoint inhibition for pancreatic cancer: is there light at the end of the tunnel?

Pancreatic adenocarcinoma (PDAC) continues to be one of the most lethal cancers. In recent years, immunotherapy using immune checkpoint inhibitors (ICIs) resulted in dramatic clinical benefits in many solid tumor types. However, PDAC patients are yet to experience the potential benefits of this treatment strategy. This article will provide a brief overview of the available data obtained with ICI-based treatments in patients with advanced PDAC. These studies illustrate that PDACs are inherently immune-cold tumors who are largely refractory to ICI-based therapy in clinical trials. Understanding and overcoming the current failures of immunotherapy through elucidating resistance mechanisms and developing novel therapeutic approaches are essential to harness the potential durable benefits of immune-modulating therapy in this setting.

Immunotherapy for ovarian cancer: a challenging endeavor

Ovarian cancer (OC) remains to be one of the most common gynecological malignancies and is characterized by a high mortality and a poor prognosis. Cytoreductive surgery and chemotherapy remain the backbone of the OC treatment, but despite this strategy most women will experience disease recurrence. For these patients there is a large unmet need for more effective therapies. Despite the compelling evidence for the fact that OC is an immunogenic tumor, studies evaluating immune checkpoint inhibitors have yielded largely disappointing results. Several therapeutic strategies are currently being studied to boost response rates to anti-PD1/PD-L1, including the addition of chemotherapy, anti-angiogenic agents, PARP inhibitors, or other immune checkpoint inhibitors. In addition to this, other immunotherapeutic approaches such as adoptive T-cell therapy, vaccines and therapeutic targeting of myeloid immune checkpoints such as the “don’t eat me” signal CD47 are also being investigated in OC. While several of these options are promising, large controlled randomized studies are still needed to implement new immunotherapeutic options into clinical practice.

Contemporary biomarker testing for non-small-cell lung cancer

In recent years, the number of approved targeted therapies for patients with advanced non-small-cell lung cancer (NSCLC) has steadily increased, making an efficient and effective molecular profiling of paramount importance in the management of NSCLC patients. To ensure that patients receive the most appropriate treatment, broad upfront molecular testing including both established and new targetable alterations should nowadays be routine practice in the diagnostic work-up of newly diagnosed patients with advanced NSCLC. Specifically for Belgium, ComPerMed guidelines recommend to test the mutational status of EGFR, KRAS and BRAF, screen for MET exon 14 skipping mutations and look for the presence of genetic fusions/rearrangements involving ALK, ROS1, RET, and NTRK1-3. These biomarkers should be analyzed in all patients with non-squamous NSCLC and in selected NSCLC patients with a squamous histology (i.e., never smokers, very young patients). Given the multitude of biomarkers that need to be tested, multigene testing using next generation sequencing (NGS) has gradually replaced sequential single gene testing as the preferred molecular screening tool in NSCLC. In fact, combined DNA/RNA NGS is now considered to be the most reliable and efficient approach for comprehensive detection of all approved and emerging biomarkers in advanced NSCLC (excluding PD-L1 detection). Both tissue samples as cytology specimens can be used for these NGS analyses as long as they contain a sufficient percentage of neoplastic cells and are processed in a way that safeguards nucleic acid integrity. In Belgium, a program is in place offering reimbursed DNA/RNA NGS testing to NSCLC patients through a network of 10 reference centers.