Javad Shahidi

Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine–cisplatin plus necitumumab versus gemcitabine–cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer

SQUIRE was a phase III study of gemcitabine and cisplatin with or without necitumumab in patients with metastatic squamous NSCLC. The majority of SQUIRE patients had EGFR protein expressing tumors. Similar to SQUIRE ITT, patients with EGFR protein expressing tumors benefitted from addition of necitumumab to chemotherapy with a safety profile consistent with that of the overall SQUIRE population.

Measuring the quality of life of people at the end of life: The McGill Quality of Life Questionnaire–Revised

Background: The McGill Quality of Life Questionnaire has been widely used with people with life-threatening illnesses without modification since its publication in 1996. With use, areas for improvement have emerged; therefore, various minor modifications were tested over time. Aim: To revise the McGill Quality of Life Questionnaire (McGill Quality of Life Questionnaire–Revised) while maintaining or improving its psychometric properties and length, keeping it as close as possible to the McGill Quality of Life Questionnaire to enable reasonable comparison with existing McGill Quality of Life Questionnaire literature. Design: Data sets from eight studies were used (four studies originally used to develop the McGill Quality of Life Questionnaire, two to develop new McGill Quality of Life Questionnaire versions, and two with unrelated purposes). The McGill Quality of Life Questionnaire–Revised was developed using analyses of measurement invariance, confirmatory factor analysis, and calculation of correlations with the McGill Quality of Life Questionnaire’s global quality of life item. Setting/Participants: Data were from 1702 people with life-threatening illnesses recruited from acute and palliative care units, palliative home care services, and oncology and HIV/AIDS outpatient clinics. Results: The McGill Quality of Life Questionnaire–Revised consists of 14 items (plus the global quality of life item). A new Physical subscale was created combining physical symptoms and physical well-being and a new item on physical functioning. The Existential subscale was reduced to four items. The revised Support subscale, renamed Social, focuses more on relationships. The Psychological subscale remains unchanged. Confirmatory factor analysis results provide support for the measurement structure of the McGill Quality of Life Questionnaire–Revised. The overall scale has good internal consistency reliability (α = 0.94). Conclusion: The McGill Quality of Life Questionnaire–Revised improves on and can replace the McGill Quality of Life Questionnaire since it contains improved wording, a somewhat expanded repertoire of concepts with fewer items, and a single subscale for the physical domain, while retaining good psychometric properties.

EGFR Gene Copy Number by FISH May Predict Outcome of Necitumumab in Squamous Lung Carcinomas: Analysis from the SQUIRE Study

Introduction: Necitumumab is a monoclonal antibody targeting EGFR. In the SQUIRE trial, the addition of necitumumab to chemotherapy for squamous cell lung cancer significantly improved overall survival (OS) (hazard ratio [HR] = 0.84); in a post hoc analysis, EGFR copy number gain determined by fluorescence in situ hybridization (FISH) showed a trend toward improved OS (HR = 0.70) and progression‐free survival (PFS) (HR = 0.71) with the addition of necitumumab. We present the analysis of granular EGFR FISH data from SQUIRE to examine the potential predictive role of high polysomy and gene amplification, as both were included in the FISH‐positive category. Methods: Available specimens from SQUIRE underwent FISH analysis in a central laboratory, and each sample was evaluated by using the Colorado EGFR scoring criteria. The correlation of granular FISH parameters with clinical outcomes was assessed. Results: Samples were available for 557 of 1093 patients; 208 patients (37.3%) were FISH‐positive, including 167 (30.0%) with high polysomy and 41 (7.4%) with gene amplification. In patients with high polysomy, the addition of necitumumab resulted in a statistically significant increase in PFS (6.08 versus 5.13 months [p = 0.044]) and nonstatistically significant increase in OS (12.6 versus 9.5 months [p = 0.133]); among patients with gene amplification, the addition of necitumumab did not significantly improve PFS (7.4 versus 5.6 months; [p = 0.334]) but did improve OS (14.8 versus 7.6 months; [p = 0.033]). Conclusions: EGFR copy number gain by FISH might have a role as a predictive biomarker for necitumumab in squamous cell lung cancer. In our opinion, these data encourage further studies to prospectively evaluate this potential biomarker.

Venous thromboembolism with EGFR monoclonal antibody necitumumab in stage IV non-small cell lung cancer: A retrospective cohort analysis

INTRODUCTION Metastatic non-small cell lung cancer (NSCLC) is a recognized risk factor for VTE. Some systemic treatments may increase this risk further. Here, we present the risk of VTE and its prognostic significance for patients treated with chemotherapy (chemo) and the EGFR monoclonal antibody necitumumab (neci) for metastatic NSCLC. METHODS Four trials of 1st-line treatment for Stage IV NSCLC were analyzed: two randomized phase 3 studies of cisplatin/gemcitabine ±neci in squamous NSCLC (SQUIRE: N = 1079) and cisplatin/pemetrexed ±neci in non-squamous NSCLC (INSPIRE: N = 616); JFCL (N = 161), a randomized phase 2 trial of carboplatin/paclitaxel ±neci in squamous NSCLC; and JFCK (N = 61), a single arm phase 2 trial of cisplatin/gemcitabine +neci in squamous NSCLC. A Cox proportional hazards model with VTE as a time-dependent covariate was used for overall survival (OS) analyses. RESULTS Neci + chemo was associated with an increased risk of VTE (Relative Risk [RR]: 1.579; 95% CI: 1.155-2.158). History of VTE (RR: 1.899; 95% CI: 1.142-3.156) and prior cardiac/cardiovascular events (RR: 1.514; 95% CI: 1.102-2.082) were associated with increased risk of VTE. Decreased VTE risk was seen with: male sex (RR: 0.696; 95% CI: 0.502-0.964), eastern European geographic region (RR: 0.387; 95% CI: 0.267-0.562) and squamous cell pathology (RR: 0.653; 95% CI: 0.483-0.883). VTE occurrence showed no association with OS (HR: 1.121; 95% CI: 0.930-1.351). CONCLUSION Our data suggest that certain patient characteristics such as prior history of VTE and non-squamous histology might be associated with an increased risk of on-treatment VTE in NSCLC, although in this study, overall survival was not affected. Further studies to develop measures for identifying high-risk patients are needed to inform treatment decisions as well as VTE management and prophylaxis.