Paola Maria Medusa

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.

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.

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.

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.