SPECIAL

ESMO develops new, living guidelines for the treatment of patients with metastatic non-small cell 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.

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.

Highlights in hormone-receptor-positive breast cancer

SABCS 2022 featured a plethora of interesting presentations in the field of hormone receptor-positive (HR+) breast cancer (BC). In the early disease setting, updated results were presented for the MonarchE trial, evaluating adjuvant abemaciclib + endocrine therapy (ET). Results were also presented for the SWOG S1207 study, assessing the addition of everolimus to adjuvant ET, together with 12-year results of TAILORx. A final early-stage study evaluated the Breast Cancer Index as a tool to select pre-menopausal patients for whom ovarian function suppression (OFS) will likely not be beneficial. In the advanced setting, the RIGHT Choice study assessed ribociclib plus ET in patients with aggressive forms of metastatic HR+ BC. Several novel treatment strategies were also evaluated in the metastatic HR+ setting. CAPItello-291 tested the AKT inhibitor capivasertib plus fulvestrant (CAPItello-291), while several other studies addressed the use of selective oestrogen receptor degraders (SERDs) in this setting. Finally, an analysis of the phase III TROPICS-2 study was presented evaluating the efficacy of Sacituzumab Govitecan in function of Trop-2 expression levels.

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