Lung cancer is one of the most common human malignancies and the leading cause of cancer-related death worldwide. Novel therapeutic approaches, like targeted therapies against specific molecular alterations and immunotherapy, have revolutionized in the last decade the oncological outcomes in patients affected by non-small cell lung cancer (NSCLC). The advent of immunotherapy for the treatment of NSCLC has significantly improved overall and progression-free survival, as well as the patient’s quality of life in comparison to traditional chemotherapy. Currently, it is estimated that long-term survival can be achieved in more than 15% of NSCLC patients treated with immunotherapy. Therefore, the optimal duration of immunotherapy in long survivors needs to be established to avoid overtreatment, side effects, and high costs and at the same time, protect them from potential disease relapse or progression. We performed a narrative review to discuss all the aspects related to the optimal duration of immunotherapy in long survivors with NSCLC. Data regarding the duration of immunotherapy in the most impacting clinical trials were collected, along with data regarding the impact of toxicities, side effects, and costs for healthcare providers. In addition, the two-year immunotherapy scheme in patients who benefit from first-line or subsequent treatment lines are examined, and the need for biomarkers that can predict outcomes during and after immunotherapy cessation in patients affected by NSCLC are discussed.

Non-small cell lung cancer (NSCLC) remains a disease with a poor prognosis despite the advances in therapies. NSCLC with actionable oncogenic alterations represent a subgroup of diseases for which tyrosine kinase inhibitors (TKIs) have shown relevant and robust impact on prognosis, both in early and advanced stages. While the introduction of powerful TKIs increases the ratio of potentially curable patients, the disease does develop resistance over time through either secondary mutations or bypass activating tracks. Therefore, new treatment strategies are being developed to either overcome this inevitable resistance or to prevent it, and proteolysis targeting chimera agents (PROTACs) are among them. They consist of two linked molecules that bind to a target protein and an E3 ubiquitin ligase that causes ubiquitination and degradation of proteins of interest. In this paper, we review the rationale for PROTAC therapy and the current development of PROTACs for oncogene-addicted lung cancer. Moreover, we critically analyze the strengths and limitations of this promising technique that may help pave the way for future perspectives.

Small cell lung cancer (SCLC) is one of the deadliest thoracic neoplasms, in part due to its fast doubling time and early metastatic spread. Historically, cytotoxic chemotherapy consisting of platinum–etoposide or anthracycline-based regimens has demonstrated a high response rate, but early chemoresistance leads to a poor prognosis in advanced SCLC. Only a fraction of patients with limited-disease can be cured by chemo-radiotherapy. Given the disappointing survival rates in advanced SCLC, new cytotoxic agents are eagerly awaited. Unfortunately, few novel chemotherapy drugs have been developed in the latest decades. This review describes the results and potential application in the clinical practice of novel chemotherapy agents for SCLC.

Non-small cell lung cancer (NSCLC) remains a dire disease being the first cause of cancer death among both genders. Early-stage NSCLC often has better treatment outcomes despite it being a highly heterogeneous disease. So far, the neo-adjuvant chemotherapy strategies have led to a small benefit with an improvement of 5% in overall survival as an absolute benefit. Recently, the introduction of immune checkpoint inhibitors combined with chemotherapy has shown robust efficacy in terms of event-free survival and overall survival. Thus, these combinations are today considered a new standard of care in early-stage NSCLC. The application of these strategies to all-comer population lead to confounding definitive results regarding the efficacy and predictive biomarkers are urgently needed balancing the promise of healing than toxicities. At present, the clinical staging TNM system guides the clinical choice, however it is not entirely sufficient. Circulant tumoral DNA (ctDNA) emerged as a promising prognostic and predictive biomarker that may guide the future perioperative strategy and pave the way to personalized medicine also in this exciting field. This narrative review aims to put in the context the employment of ctDNA, give some perspective and suggestions weighing the pros and cons of this technique for our tomorrow clinical practice.

The incidence of cancer-associated thrombosis has increased in recent years. While the association between venous thromboembolism (VTE) and chemotherapy is well established, there is no clear link between immune checkpoint inhibitors (ICIs) and VTE risk. Many risk assessment models (RAMs) have been developed to identify high-risk patients who need prophylaxis. However, these models are validated in patients undergoing chemotherapy, while they are scarce in those receiving immunotherapy. Moreover, the mechanisms linking ICIs to thrombosis are still a matter of debate. They include the upregulation of pro-inflammatory intracellular pathways, the release of cytokines, the activation of innate immune cells, the release of tissue factors and platelet activation, and the increase in adhesion molecules, thus resulting in the recruitment of agents involved in coagulation. Promising biomarkers are emerging to identify patients undergoing ICIs who are at high risk of developing VTE and need prophylaxis. In this review we investigate the possible causation between cancer-associated thrombosis (CAT) and immunotherapy and the underlying pathophysiological mechanisms. Thus, we suggest the most appropriate therapeutic approaches based on currently available data.

Background: The treatment landscape for non-small cell lung cancer (NSCLC) has evolved significantly with the advent of immunotherapy. Nonetheless, uncertainty regarding optimal first-line treatments, special populations, and the feasibility of rechallenge remains. This study aims to investigate Italian oncologists’ opinions on these aspects through a Delphi Survey. Methods: A steering committee (SC) of six oncologists identified three topics of interest, namely NSCLC (first line) therapeutic choice, NSCLC special populations, and NSCLC immunotherapy rechallenge), and drafted several topic-related statements to be voted in the Delphi Survey by the 61 oncologists forming the Delphi Panel. The survey included two rounds, wherein the experts rated their agreement/disagreement with the statements on a 5-point Likert scale. Consensus was defined as agreement/disagreement by at least 75% of the panel. Results: The SC drafted 69 statements for the first round, of which 16 (23.2%) met the agreement threshold, 5 (7.2%) met the disagreement threshold, and 48 (69.6%) did not reach consensus. The SC revised the latter statements and drafted 37 for the second round. Overall, 5 (13.5%) statements met the agreement threshold, 1 (2.7%) met the disagreement threshold, and 31 (83.8%) did not reach consensus in the second round. Conclusions: The survey showed agreement on the necessity of molecular characterization, mutations, smoke, the role of steroid therapy, and immunotherapy rechallenge, and revealed several areas of uncertainty among Italian oncologists on the use of immunotherapy in NSCLC. Statements—where consensus was not met—can be used to guide future clinical research in resolving the issues.