Oligometastatic non-small cell lung cancer (NSCLC) represents a separate entity with a different biology and prognosis compared to stage IV NSCLC. Challenges range from the very definition of oligometastatic disease to the timing and techniques of local treatments, and their benefit in prolonging patient survival. Most of the international consensus and guidelines agree on the need for shared criteria, such as appropriate stadiation and even tissue biopsy if needed, in order to select patients that could really benefit from personalised strategies. Multidisciplinary evaluation is crucial in order to define if every lesion is amenable to radical local treatment, which appears to be the most important criterion across different guidelines. A distinction must be made depending on the time of oligo-disease detection, separating de novo oligometastatic disease from oligorecurrence, oligoprogression and oligoresidual disease. These separate entities imply a different biology and prognosis, and treatment strategies consequently must be tailored. Locoregional approaches are therefore often contemplated in order to ensure the best outcome for the patient. In non-oncogene-addicted disease, the advent of immune checkpoint blockers (ICBs) allows physicians to take into consideration consolidative treatments, but timing, technique and subsequent systemic treatment remain open issues. In oncogene-addicted NSCLC, local treatments are nowadays preferably reserved to cases of oligoprogression, but the advent of new, more potent drugs might challenge that. In this review, we summarised the current knowledge, consensuses and data from retrospective and prospective trials, with the aim of shedding some light on the topic and emphasising the unmet clinical need.

Antibody–drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), trophoblast cell surface antigen 2 (TROP2), Mesenchymal–epithelial transition factor (c-MET), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs. In this review, we describe the structures and mechanism of action of different ADCs; we present the evidence derived from the main clinical trials investigating ADCs’ efficacy, focusing also on related toxicity; and, finally, we discuss future perspectives in terms of toxicity management, possible biomarkers, and the identification of resistance mechanisms.

The role of adjuvant therapy in stage III melanoma is well established in clinical practice. Because stage IIB–IIC melanoma carries a risk of recurrence and melanoma-specific mortality comparable to that of stage III disease, adjuvant approaches have also been developed for patients with thick stage II tumors. Both pembrolizumab and nivolumab have demonstrated efficacy in reducing the risk of local and distant recurrence in patients with high-risk stage II melanoma, whereas evidence supporting the use of BRAF-MEK inhibitors in this setting remains inconclusive. Combinations of immune checkpoint inhibitors, as well as immunotherapy combined with mRNA-based vaccines, are currently under investigation in clinical trials. However, given the non-trivial risk of immune-related adverse events, careful selection of patients with stage II disease who are most likely to derive meaningful benefit from adjuvant therapy is essential. In this context, several clinicopathologic variables and gene expression profiling-based prognostic tools have been proposed to refine risk stratification. To date, however, none of these instruments have been incorporated into routine clinical practice, and no validated predictive biomarkers are available. Accordingly, optimal patient selection for adjuvant therapy remains an important unmet clinical need in early-stage melanoma.