T. Feys MBA, MSc

Highlights in breast cancer

ASCO 2021 featured one crucial, practice-changing trial in early breast cancer: the OlympiA trial showed that one year of adjuvant olaparib improves invasive disease-free survival by 8.8% compared to placebo, when administered to high risk early breast patients (triple negative or hormone sensitive and HER2 negative) with a germline BRCA1 or 2 mutation. Furthermore, ECOG-ACRIN EA1131 failed to show improved outcome in triple negative breast cancer treated without pathological complete response after neoadjuvant chemo-therapy with platinum based chemotherapy compared to the current standard capecitabine. GeparNUEVO for the first time showed long term outcome with anti-PD(L)1 therapy administered with neoadjuvant chemotherapy in triple negative breast cancer. In the advanced setting, interesting overall survival updates of the PALOMA-3 and MONALEESA-3 studies were presented. Furthermore, the SYsucc-002 trial demonstrated that trastuzumab plus endocrine therapy was non-inferior to and had fewer toxicities compared with trastuzumab plus chemotherapy in patients with HR+/HER2- metastatic breast cancer. In addition, this article will touch upon several other studies that are notable.

(BELG J MED ONCOL 2021;15(5):208-17)

Highlights in respiratory oncology

At ASCO 2021 much of the attention in the field of lung cancer went to early-stage non-small cell lung cancer (NSCLC) discussing both (neo)adjuvant strategies and local treatment modalities. In metastatic NSCLC, we would like to highlight some recent (chemo)immunotherapeutic advances in the treatment of non-oncogene addicted tumours as well as promising strategies to overcome osimertinib resistance, targeting of KRAS G12C mutated tumours and updated results for EGFR exon 20, HER2 exon 20, MET and RET targeting. As a final abstract, the results of the randomised phase III CALGB 30610/RTOG 0538 trial evaluating high-dose thoracic radiotherapy in small cell lung cancer will be summarised. We would like to acknowledge Prof. Veerle Surmont (University Hospital Ghent) for her help in selecting the abstracts discussed in this overview.

Highlights in gastro-intestinal cancers

At ASCO 2021, the most important studies in gastro-intestinal (GI) cancer related to the use of immuno-therapy in cancers of the upper gastro-intestinal tract. For advanced oesophageal squamous cell carcinoma (ESCC), the CheckMate 648 trial demonstrated that both nivolumab plus chemotherapy and nivolumab plus ipilimumab represent a new potential first-line standard of care, especially for patients with a tumour PD-L1 expression of at least 1%. For adenocarcinoma of the oesophagus and oesophago-gastric junction, there is no evidence that peri-operative chemotherapy is unacceptably inferior to multimodal therapy. For tumours of the lower gastro-intestinal tract, the most important results came from the DESTINY-CRC01, CHRONOS, FIRE-4.5 and PANAMA studies.

(BELG J MED ONCOL 2021;15(5):248-53)

New oncology reimbursementsin Belgium

OVERVIEW OF BELGIAN REIMBURSEMENT NEWS

(BELG J MED ONCOL 2021;15(5):264-5)

Immunotherapy as first-line treatment for metastatic NSCLC

The added value of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibition as first-line treatment in non-oncogene addicted metastatic non-small cell lung cancer (NSCLC) is supported by substantive scientific evidence and clinical experience. In the absence of a true contra-indication, the use of immune checkpoint inhibitors (ICIs) is recommended as first-line therapy in phase IV NSCLC patients without targetable oncogenic driver. However, a growing challenge in clinical practice consists of the choice for one of the available first-line anti-PD-(L)1-based treatment options. The main decision in this respect consists of the choice whether to use single agent anti-PD-(L)1 therapy, or go for one of the available combination strategies.

Targeted therapies for non-metastatic NSCLC

Approximately a quarter of patients with non-small-cell lung cancer (NSCLC) is being diagnosed in an early stage of the disease and are amenable for a radical surgery. Despite radical surgery, the five-year survival rates for fully resected early stage NSCLC remains rather disappointing. To address this, several studies have assessed the use of adjuvant chemotherapy in an attempt to reduce the recurrence rate after surgery. Unfortunately, how-ever, the survival benefit obtained from adjuvant chemotherapy is somewhat modest, with approximately half of patients suffering a disease relapse. The identification of reliable predictive biomarkers for a response to targeted agents in the metastatic setting, the design of molecularly oriented studies, and the availability of novel potent and less toxic agents paves the way for the evaluation of these targeted agents in the (neo)adjuvant treatment of patients with earlier-stage NSCLC harboring an oncogenic driver mutation. The results obtained with this therapeutic strategy will be summarized in this article.

New therapeutic targets in patients with advanced NSCLC

A better understanding of critical molecular and cellular mechanisms driving tumor initiation, maintenance, and progression in non-small-cell lung cancer (NSCLC) has led to the discovery of a variety of novel drug targets and the development of new treatment strategies. Since the introduction of tyrosine kinase inhibitors (TKIs) targeting mutant EGFR, we have witnessed a continued shift towards a biomarker-driven treatment algorithm for patients with advanced-stage NSCLC. The identification of less common oncogene drivers led to a marked reshaping of the diagnostic and therapeutic approach towards NSCLC. The introduction of novel highly selective inhibitors is expanding the use of targeted therapies to rare and ultra-rare subsets of patients, further increasing the therapeutic armamentarium of advanced NSCLC. In this article we will briefly discuss the recent advances for the targeted treatment of advanced NSCLC patients with RET fusions, MET exon14 skipping, HER2 overexpression and KRAS mutations.