Zoi Tsourti

Randomized phase III trial of erlotinib versus docetaxel in patients with advanced squamous cell non-small cell lung cancer failing first line platinum-based doublet chemotherapy stratified by Veristrat good versus Veristrat poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung trial.

Introduction Docetaxel and erlotinib are registered second‐line treatments for wild‐type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second‐line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS‐lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. Methods EMPHASIS‐lung was a randomized phase III multicenter trial exploring the differential effect of second‐line erlotinib versus docetaxel on progression‐free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC. Results A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events. Conclusions The final analysis of EMPHASIS‐lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study).

Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

INTRODUCTION In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome. METHODS Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells. A total of 182 MET IHC+ and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation. RESULTS MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN≥5 in 4.1% of 1572 patients. MET amplification and MET GCN≥5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (p<0.001). METex14 skipping mutation prevailed in 5 of 182 (2.7%) MET IHC+ WT EGFR/KRAS NSCLC, 4 of which within the 88 adenocarcinomas (4.5%). No association of IHC MET overexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR. CONCLUSION MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice.

Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase and Tensin Homolog Immunohistochemistry — Clinical Associations in NSCLC Patients of the European Thoracic Oncology Platform Lungscape Cohort

Introduction: Phosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3‐kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value. Methods: After an external quality assessment using SP218, 138G6 and 6H2.1 anti‐PTEN antibodies, scored on webbook and tissue microarray, the European Thoracic Oncology Platform cohort samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with SP218. All cores were H‐scored by pathologists and by computerized pixel‐based intensity measurements calibrated by pathologists. Results: All three antibodies differentiated six PTEN+ versus six PTEN‐ cases on external quality assessment. For 138G6 and SP218, high sensitivity and specificity was found for all H‐score threshold values including prospectively defined 0, calculated 8 (pathologists), and calculated 5 (computer). High concordance among pathologists in setting computer‐based intensities and between pathologists and computer in H‐scoring was observed. Because of over‐integration of the human eye, pixel‐based computer H‐scores were overall 54% lower. For all cutoff values, PTEN‐ was associated with smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In adenocarcinomas, PTEN‐ was associated with poor survival. Conclusion: Calibration of immunoreactivity intensities by pathologists following computerized H‐score measurements has the potential to improve reproducibility and homogeneity of biomarker detection regarding epitope validation in multicenter studies.

Report on the status of women occupying leadership roles in oncology

Background While the global workforce is approaching gender parity, women occupy a small number of management level positions across most professions, including healthcare. Although the inclusion of women into the membership of many oncology societies has increased, the under-representation of women in leadership roles within international and national oncology societies remains relatively consistent. Moreover, the exact status of women participating as board members or presidents of oncology societies or as speakers at oncology congresses was undocumented to date. Methods The database used in this analysis was derived from data collection performed by the European Society for Medical Oncology for the years 2015–2016 and data analyses performed using the Statistical Analysis Software V.9.3 and R language for statistical computing V.3.4.0 by Frontier Science Foundation-Hellas. The literature search was performed by the authors. Results We report the presence of a gender gap within oncology. Results regarding the under-representation of women occupying leadership roles in oncology show female participation as members of the board or presidents of national and international oncology societies and as invited speakers at oncology congresses remains below 50% in the majority of societies included in this analysis. Women in leadership positions of societies was associated with a higher percentage of female invited speakers at these societies’ congresses (p=0.006). Conclusion The full contribution that can be attained from using the potential of women in leadership roles is currently under-realised. Examples of how gender and minority participation in organisations improves outcomes and creativity are provided from science, clinical practice and industry that show outcomes are greatly improved by collective participation of both men and women. Although there are programmes in place in many oncology organisations to improve this disparity, the gender gap is still there. Ongoing discussion may help to create more awareness in the effort to accelerate the advancement of women within oncology.

Gender-related challenges facing oncologists: the results of the ESMO Women for Oncology Committee survey

Background Although women account for a growing proportion of the oncology workforce, there is evidence they are under-represented in leadership roles. To gain further insights into this issue and extend understanding of gender challenges, the European Society for Medical Oncology Women for Oncology (W4O) Committee undertook a survey of female and male oncologists in 2016. Design The 2016 W4O questionnaire included questions on (1) Demographics and professional environment, (2) Gender impact on career development, (3) Challenges for career progression and inappropriate behaviour experienced in the workplace, (4) Barriers for gender parity and (5) The gender gap. Between July and September 2016, the online survey was available to male and female clinical and academic oncology healthcare professionals in the EU and internationally. Results Responses were analysed from 462 oncologists, of whom 76.7 % were women. Of female respondents, 45.5 % had a managerial or leadership role, compared with 65 % of male respondents (p<0.001). Men were more likely to have leadership roles, even in clinical teams with more women than men. Women respondents were more likely to consider their gender had a major impact on their career than men: 35.9 % vs 20.9 % (p<0.001). The biggest challenge to career progression for women was work and family balance (64.2%). Of female respondents, 14.4 % believed there had been significant or major progress in closing the gender pay gap compared with 39.3 % of men (p<0.001). Of female participants, 37.7 % reported they had encountered unwanted sexual comments by a superior or colleague. Conclusions New initiatives are needed to address under-representation of women oncologists in leadership roles, including greater and concrete promotion of work–life balance, development and leadership training for women, and more support for flexible working. The fact that over a third of women in the survey had encountered unwanted sexual comments at work is of great concern and must be urgently addressed.