Immunotherapy for non-small-cell lung cancer: the past 10 years.

ABSTRACT In the past decade, the approach to patients with metastatic non-small-cell lung cancer has relied on chemotherapy and on targeted agents for molecularly selected subgroups of patients. Recent work has introduced immunotherapy as another area of progress, and likely as a new treatment paradigm in the near future. While the large Phase III studies with cancer vaccination with the current technologies remain at present disappointing, the immunomodulation strategies with immune checkpoint inhibitors have delivered remarkable results in expanded Phase I studies and are now intensively studied in large Phase III studies. This review summarizes the past decade of immunotherapy for non-small-cell lung cancer, gives an updated overview of trials in this field, and the context of future development in this exciting field.

Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy.

ABSTRACT: Immune checkpoint inhibition has improved the clinical outcomes for numerous patients with cancer. However, the downside is a whole new spectrum of immune-related adverse events. We report a 68-year-old man with a history of nonsmall cell lung cancer presenting with a spontaneous corneal perforation in the right eye after 22 cycles of pembrolizumab. In addition, a chronic central nonhealing epithelial defect developed after performing a penetrating keratoplasty. Treatment with autologous serum drops resulted in complete healing of the corneal ulcer, where other conventional therapies had no effect. One month after reinitiating pembrolizumab therapy, our patient presented again with a corneal perforation in the fellow eye. This case describes relapsing sterile ulcerations associated with pembrolizumab use and presents an unexpected cure.

Prognostic Value and Reproducibility of AI-assisted Analysis of Lung Involvement in COVID-19 on Low-Dose Submillisievert Chest CT: Sample Size Implications for Clinical Trials.

PURPOSE: To compare the prognostic value and reproducibility of visual versus AI-assisted analysis of lung involvement on submillisievert low-dose chest CT in COVID-19 patients. MATERIALS AND METHODS: This was a HIPAA-compliant, institutional review board-approved retrospective study. From March 15 to June 1, 2020, 250 RT-PCR confirmed COVID-19 patients were studied with low-dose chest CT at admission. Visual and AI-assisted analysis of lung involvement was performed by using a semi-quantitative CT score and a quantitative percentage of lung involvement. Adverse outcome was defined as intensive care unit (ICU) admission or death. Cox regression analysis, Kaplan-Meier curves, and cross-validated receiver operating characteristic curve with area under the curve (AUROC) analysis was performed to compare model performance. Intraclass correlation coefficients (ICCs) and Bland- Altman analysis was used to assess intra- and interreader reproducibility. RESULTS: Adverse outcome occurred in 39 patients (11 deaths, 28 ICU admissions). AUC values from AI-assisted analysis were significantly higher than those from visual analysis for both semi-quantitative CT scores and percentages of lung involvement (all P<0.001). Intrareader and interreader agreement rates were significantly higher for AI-assisted analysis than visual analysis (all ICC ≥0.960 versus ≥0.885). AI-assisted variability for quantitative percentage of lung involvement was 17.2% (coefficient of variation) versus 34.7% for visual analysis. The sample size to detect a 5% change in lung involvement with 90% power and an α error of 0.05 was 250 patients with AI-assisted analysis and 1014 patients with visual analysis. CONCLUSION: AI-assisted analysis of lung involvement on submillisievert low-dose chest CT outperformed conventional visual analysis in predicting outcome in COVID-19 patients while reducing CT variability. Lung involvement on chest CT could be used as a reliable metric in future clinical trials.

Does nivolumab for progressed metastatic lung cancer fulfill its promises? An efficacy and safety analysis in 20 general hospitals.

OBJECTIVES: In patients with refractory or recurrent non-small-cell lung cancer (NSCLC) after first line chemotherapy, phase III trials showed superiority of nivolumab, an IgG4 programmed death-1 immune-checkpoint-inhibitor antibody, over docetaxel. We evaluated case mix, effectiveness and safety of nivolumab upon implementation in general practice. MATERIALS AND METHODS: In 20 general hospitals, all consecutive NSCLC patients treated with nivolumab within the medical need program (inclusion period 12 months) in Flanders - Belgium were evaluated. RESULTS: There were 267 patients, Eastern Cooperative Oncology Group (ECOG) score was 2 in 24% and 0-1 in 76%. In 48%, two or more systemic regimens were given before nivolumab. The median overall survival was 7.8 months (95% confidence interval (CI) 6.3-9.3). At one year, the overall survival rate was 36.5±0.34%. Median progression-free survival was 3.7 months (95% CI 2.9-4.5). An objective response was obtained in 23.2%. ECOG score 2 and presence of liver metastasis strongly correlated with worse survival (p<0.00001). Treatment related adverse events grade 3 or 4 were reported in 21%, colitis (4%) and pneumonitis (7%) were most frequent. CONCLUSION: Upon implementation of nivolumab therapy in general hospitals, the case mix was characterized by a more heavily pretreated population with a substantial fraction of patients with ECOG score 2. The median overall survival is slightly inferior to what was published in the randomized phase III trials. An ECOG score 2 and the presence of liver metastasis correlated strongly with a worse survival. We report a high prevalence of serious adverse events.