Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.

Non‐small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancer cases. Stage III NSCLC represents a highly heterogenous stage characterized by different disease presentations and a wide range of treatment options. For patients with good performance status and unresectable-stage III NSCLC with programmed death-ligands 1 (PD-L1) tumor proportion score (TPS) ≥1%, durvalumab consolidation immunotherapy after a platinum-based chemo-radiotherapy is strongly recommended. However, age, poor performance status, underlying comorbidities may represent contraindications for chemotherapy to be used in a subgroup of patients. Herein, we report a case of an 80-year-old male affected by a stage IIIB lung adenocarcinoma with overexpression of PD-L1 (TPS 90%) treated with pembrolizumab, an immune checkpoint inhibitor targeting PD-1/PD-L1 pathways, which shows a complete resolution of lung lesion after four cycles of treatment. Although randomized controlled trials are required, this case report may suggest the potential role of pembrolizumab for chemotherapy unsuitable patients with overexpressing PD-L1 unresectable-stage III NSCLC.

Background: Small cell lung cancer (SCLC) is a malignant carcinoma characterized by high proliferative rate and early metastatization with limited treatment options and poor prognosis. The approval of ICIs has established a new standard of care for extensive-stage (ES)-SCLC (5). Atezolizumab, an anti PD-L1 monoclonal antibody, has been the first immune checkpoint inhibitor (ICI) to be approved for SCLC patients. This study aims to retrospectively evaluate the real-world effectiveness and safety of atezolizumab in a cohort of patients with ES-SCLC. Methods: We conducted a monocentric retrospective analysis of SCLC patients who received atezolizumab in addition to chemotherapy, between January 2020 and December 2023. Study design endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Results: A total of 134 patients were included in this study. Out of 134 patients who began the CEA protocol, 100 continued maintenance. Currently, 25 are alive, 17 still on atezolizumab, 5 on second-line therapy, and 3 receiving best supportive care. The median age was 65 years. Patients received a median of four cycles of CEA (range 1–6 cycles), while the median number of atezolizumab maintenance cycles was eight (range 0–75). The overall median survival was 15 months, with patients who received more than 30 cycles of atezolizumab showing OS of 46.7% at 48 months. Common adverse events included skin disorders, pneumonitis, colitis, alanine, and aspartate deaminase increment, dysthyroidism, and blood disorders with only 3% of patients experiencing grade 3 or higher toxicities. Conclusions: In this real-world cohort, atezolizumab demonstrated comparable effectiveness to clinical trial results, with a manageable safety profile. These findings support the use of atezolizumab as a viable treatment option for ES-SCLC in routine clinical practice.

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring.

Stage III unresectable non-small cell lung cancer (NSCLC) represents a heterogeneous group, for which consolidation immunotherapy with durvalumab, after chemo-radiotherapy, is currently considered the standard of treatment by all national and international guidelines, based on data from the PACIFIC trial. Regarding adverse reactions, pulmonary toxicities represent the most difficult to diagnose and manage. It is planned to include 123 patients at 28 sites in Southern Italy experiencing lung cancer in this observational study. The recruitment phase is scheduled to last 24 months (from October 1, 2024, to October 1, 2026) and the followup phase is scheduled to last 24-36 months after durvalumab discontinuation. Retrospective data collection can be considered from 09/01/2023. The duration of the study will be 60 months. We propose to estimate the incidence and grading of pulmonary toxicity from radiation therapy and immunotherapy, according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and to investigate the correlation of pulmonary toxicity with pulmonary function tests (PFTs), with a particular focus on forced expiratory volume in one second (%FEV1) and forced vital capacity (%FVC) based on spirometry, diffusing capacity of the lung for carbon monoxide (%DLCO), partial pressure of arterial oxygen (PaO2) based on arterial blood gas (ABG) sampling and maximal distance that patients can walk at their own pace in 6 min and minimal oxygen saturation (SpO2) during the 6-minute walking test (6MWT). Pulmonary function tests (basal spirometry, DLCO, 6MWT, ABG) are evaluated at Time 0 (baseline), at Time 1 (post- RT), at Time 2 (after 6 cycles of immunotherapy) and at Time 3 (end of treatment). At data cut-off (31 mar 2025), 45 patients were enrolled and 10 patients were screened failure. Among the 45 patients enrolled, there were 7 cases of pulmonary toxicity (15.5 %). All of the cases showed post-actinic pneumonia (4 cases of grade 2, 2 cases of grade 3 and one case of grade 4 pneumonia). PRELUDIO trial is a study in stage III NSCLC undergoing consolidation immunotherapy with durvalumab, after chemo-radiotherapy, with the aim to estimate the incidence and grading of pulmonary toxicity according to CTCAE and to investigate the correlation of pulmonary toxicity with pulmonary function tests (PFTs), performed per clinical practice.