J. Blokken PhD, PharmD

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)

Breast cancer task force

In line with the tradition, the 2023 annual BSMO meeting kicked off with a session from the Breast Cancer Task Force. Prof. Evandro de Azambuja (Institut Jules Bordet, Brussels) opened the session with a lecture on the extended use of adjuvant endocrine therapy and the impact of recent insights on clinical practice. Thereafter, Dr. Donatienne Taylor (Clinique Sainte-Elisabeth CHU UCL Namur, Namur) discussed the antibodydrug conjugate landscape in advanced breast cancer. Finally, Dr. Caroline Duhem (Centre Hospitalier de Luxembourg, Luxemburg) shared her knowledge and experiences with the emerging adjuvant treatment escalation options in early HR+/HER2- breast cancer

Highlights in HER2-positive breast cancer

For patients with early-stage Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC), the most important data presented at SABCS 2022 consisted of the final results of the phase III PEONY study. Results of this trial add to the existing body of evidence demonstrating the benefit of the pertuzumabtrastuzumab-docetaxel regimen in patients with HER2-positive early breast cancer (EBC). In the metastatic setting, trastuzumab deruxtecan (T-DXd) was once again the center of the attention with the presentation of data from the DESTINY-Breast02, DESTINY-Breast03 and ROSET-BM trials. Finally, several studies assessed the possibility of chemotherapy-free regimens for the treatment of HER2-positive, hormone receptor (HR)- positive metastatic BC.

HER2-low breast cancer: a separate entity?

About 60% of breast cancers traditionally categorised as HER2-negative in fact express low levels of HER2 (defined as tumours with HER2 IHC expression 1+ or 2+ without HER2 gene amplification). Last year, the DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd), in patients whose tumours are not conventionally HER2+, but defined as HER2-low. As a result, HER2-low has become a clinically relevant HER2 status among patients with breast cancer, warranting a better understanding of this disease entity. As such, it was no surprise to see that at SABCS 2022, a special session was entirely devoted to HER2-low disease. Below, some key presentations of this session are summarized.

Advances in local therapy for patients with early-stage breast cancer

During SABCS 2022, several abstracts were dedicated to advances in local therapy for patients with earlystage breast cancer (BC). A first trial assessed the impact of breast conserving therapy on local recurrence in patients with multiple ipsilateral BC. Next, the OPBC-04/EUBREAST-06/OMA study evaluated the oncological outcomes following sentinel lymph node biopsy or targeted axillary dissection after downstaging with neoadjuvant chemotherapy. In addition to this, POLAR was identified as a genomic classifier that is not only prognostic for locoregional recurrence but also predictive for a benefit of radiotherapy. Finally, hypofractionated regimens of radiotherapy were studied