Amivantamab Compared with Real-World Physician's Choice after Platinum-Based Therapy from a Pan-European Chart Review of Patients with Lung Cancer and Activating EGFR Exon 20 Insertion Mutations.

Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data.

Gender inequity in the medical profession: the women doctors in Spain (WOMEDS) study.

BACKGROUND: The long-standing underrepresentation of women in leadership positions in medicine is well-known, but poorly documented globally. There is some evidence of the gender gap in academia, medical society leadership, or specific problems in some specialties. However, there are no investigations analyzing all medical specialties together and reporting the glass ceiling from a 360º perspective that includes positions in academia, research, professional organizations, and clinical activity. Additionally, the majority of studies have a US perspective, and we wonder if the perspective of a European country might be different. The WOmen in MEDicine in Spain (WOMEDS) project ( https://womeds.es ) aims to describe and characterize, in a systematic and detailed way, the gender bias in the medical profession in Spain in order to monitor its evolution over time and contribute to prioritizing gender policies. METHODS: We retrieved data for the calendar years 2019-2021 from several sources and selected surveys. We built four groups of indicators to describe leadership positions in the medical profession: (i) leadership in healthcare according to specialty and region; (ii) leadership in scientific and professional bodies; (iii) academic career; and (iv) leadership in clinical research activity. As a summary measure, we reported the women ratios, calculated as the percentage of women in specific top positions divided by the percentage of women in the relevant population. RESULTS: We found gender inequity in leadership positions in all four settings. During the observed period, only 27.6% of the heads of departments in hospitals were women compared to 61.1% of women in medical staff. Ten of the 46 medical societies grouped in the Spanish Federation of Medical Societies (FACME) (21.7%) had a women president at some point during the study period, and only 4 annual congresses had ratios of women speakers higher than 1. Women were over-represented in the lower positions and underrepresented in the top academic ones. Only 26% and 27%, respectively, of the heads of departments and deans were women. The applications for public funding for research projects are led by women only in 45% of the cases, and the budget granted to women in public calls was 24.3% lower than that of men. CONCLUSION: In all the areas analyzed, the leadership positions are still mostly occupied by men despite the feminization of medicine in Spain. The severe gender inequity found calls for urgent interventions within a defined time horizon. Such measures must concern all levels, from national or regional regulation to changes in organizational culture or incentives in specific organizations.

RESUMEN EN ESPAÑOL: ANTECEDENTES: La prolongada infrarrepresentación de las mujeres en los puestos de liderazgo en medicina es bien conocida, pero está poco documentada de forma global. Hay evidencia sobre la brecha de género en la universidad, en el liderazgo en sociedades médicas o en determinadas especialidades. Sin embargo, no hay investigaciones que analicen el techo de cristal de cada una de las especialidades médicas desde una perspectiva 360º que incluya el liderazgo en la universidad, en la investigación con fondos públicos, en la representación en sociedades científicas y colegios profesionales y en la actividad clínica. Además, la mayoría de los estudios tienen una perspectiva estadounidense y nos preguntamos si la perspectiva de un país europeo podría ser diferente. El proyecto Mujeres en Medicina en España (WOMEDS) ( https://womeds.es ) tiene como objetivo describir y caracterizar de forma sistemática y detallada sesgo de género en la profesión médica en España, para monitorizar su evolución en el tiempo y contribuir a priorizar las políticas de género. MéTODOS: Construimos cuatro grupos de indicadores sobre liderazgo de mujeres médicos: (i) en la asistencia sanitaria; (ii) en las organizaciones científicas y profesionales; (iii) carrera académica, y; and (iv) l en la investigación basándonos en datos públicos y resultados de encuestas propias s referidas a los años 2019­2021. Como medida de análisis, calculamos los ratios de mujeres, definidos como el porcentaje de mujeres en puestos altos específicos dividido por el porcentaje de mujeres en la población relevante. RESULTADOS: Encontramos un sesgo de género en los cuatro ámbitos. Durante el periodo observado, solo el 27.6% de los jefes de servicio de los hospitales eran mujeres, frente al 61.1% de mujeres en la plantilla. Diez de las 46 sociedades médicas agrupadas en la Federación de Asociaciones Científico Médicas Españolas (FACME) (21.7%) tuvieron una mujer como presidente en algún momento del periodo de estudio y sólo 4 congresos anuales tenían ratios de mujeres ponentes superiores a 1. Las mujeres estaban sobrerepresentadas en los cargos inferiores e infrarrepresentadas en los cargos académicos superiores. Sólo el 26% y el 27%, respectivamente, de los jefes de departamento y decanos eran mujeres. La solicitud de proyectos de investigación con financiación pública fue liderada por mujeres en un 45% de los casos y la financiación media de los proyectos concedidos a las mujeres fue un 24.3% inferior a la de los hombres. CONCLUSIóN: En todos los ámbitos analizados, las posiciones de liderazgo siguen siendo mayoritariamente ocupada por varones a pesar de la feminización de la medicina. Para cambiar esto, será necesario tomar medidas, tanto regulatorias -a nivel nacional y nacional regional como promover cambios en la cultura organizativa o en los incentivos en organizaciones concretas.

A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma.

Background Fibroblast growth factors (FGFs) have a fundamental role in cancer. Sequestering FGFs with GSK3052230 (FP-1039) blocks their ability to activate FGFRs while avoiding toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Methods A multicenter, open-label, phase Ib study evaluated weekly GSK3052230 added to pemetrexed/cisplatin in patients with treatment-naive, unresectable malignant pleural mesothelioma. Doses were escalated according to a 3 + 3 design, followed by cohort expansion at the maximum tolerated dose (MTD). Endpoints included safety, overall response rate, progression-free survival, and pharmacokinetics. Results 36 patients were dosed at 10, 15, and 20 mg/kg doses of GSK3052230. Three dose-limiting toxicities were observed at 20 mg/kg and one at 15 mg/kg. The MTD was defined as 15 mg/kg and used for cohort expansion. The most common treatment-related adverse events (AEs) were nausea (56%), decreased appetite (36%), infusion reactions (36%), decreased neutrophil counts (36%), and fatigue (33%). The confirmed ORR was 39% (95% CI: 23.1-56.5) (14/36 PRs) and 47% had stable disease (17/36), giving a disease control rate of 86%. At 15 mg/kg GSK3052230 (n = 25), the ORR was 44% (95% CI: 24.4-65.1), and the median PFS was 7.4 months (95% CI: 6.7-13.4). Four patients had disease control for over 1 year, and three were still ongoing. Conclusion At 15 mg/kg weekly, GSK3052230 was well tolerated in combination with pemetrexed/cisplatin and durable responses were observed. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

Metronomics for thymic carcinoma.

Although thymomas are the most frequent primary tumours of the anterior mediastinum, thymic carcinoma is very infrequent and more aggressive. Combination chemotherapy is the first-line treatment for the advanced stages, but because of the lack of evidence from randomised trials, the management of the successive lines is a challenging field. We report a partial radiological response in the seventh line of a thymic carcinoma stage IV with an oral regimen.