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.

[Clinical characteristics of neurocysticercosis from a reference hospital of the northern of Peru. 2016-2018]. / Características clínicas de la neurocisticercosis en un hospital referencial del norte del Perú. 2016-2018.

Backgound: Neurocysticercosis (NCC) is the most common parasitosis of the central nervous system, and a very important cause of epilepsy. AIM: To describe the clinical features of patients with NCC attending a high level hospital from Lambayeque during: 2016-2018. METHODS: The medical records of patients with NCC were reviewed, and their information was collected on a data sheet. RESULTS: 46 stories met the inclusion criteria; 23 patients were male, the median age was 46.5 years (IQR: 26.5-63), the youngest patient was 7 years old, and the longest 85. Thirty patients were from Lambayeque. Epilepsy occurred in 24 patients, intracranial hypertension in 10, psychic syndrome in 2 and focal neurological deficit and visual syndrome in 1; there was one asymptomatic patient and seven had epilepsy and another syndrome. In neuroimaging, cerebral calcifications were the most common lesions; 9 patients had subarachnoid cysts. Serology (western blot) was performed in 20 patients being positive in 11; 38 were definitive NCC and 8 probable. Eighteen patients received only symptomatic treatment, 27 antiparasitic treatment and 6, additionally neurosurgical treatment. Only one patient died. CONCLUSIONS: The symptoms and neuroimaging findings were proteiform and the mortality found was low.

An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer.

OBJECTIVES: GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients. METHODS AND METHODS: Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment. RESULTS: Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B. CONCLUSION: GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

Características clínicas de la neurocisticercosis en un hospital referencial del norte del Perú. 2016-2018 / Clinical characteristics of neurocysticercosis from a reference hospital of the northern of Peru. 2016-2018

INTRODUCCIÓN: La neurocisticercosis (NCC) es la parasitosis más común del sistema nervioso central, siendo una causa muy importante de epilepsia. OBJETIVO: Describir las características de pacientes con NCC atendidos en un hospital de alta complejidad de Lambayeque durante el período 2016-2018. PACIENTES Y MÉTODOS: Se revisaron las historias clínicas de pacientes con diagnóstico de NCC y se recolectó su información en una ficha de datos. RESULTADOS: 46 historias cumplieron criterios de inclusión; 23 correspondían a varones, la mediana de edad fue 46,5 años (RIC: 26,5-63), el paciente más joven tuvo 7 años, el más longevo 85 años; 30 procedían de la región Lambayeque. Epilepsia se presentó en 24 pacientes, hipertensión endocraneal en 10, síndrome psíquico en dos, déficit neurológico focal en 1, síndrome visual en 1, un paciente fue asintomático. Siete pacientes tuvieron epilepsia y otro síndrome simultáneamente. En las neuroimágenes, las calcificaciones cerebrales fueron las lesiones más comunes; 9 tuvieron quistes sub-aracnoideos. En 20 pacientes se efectuó serología por western blot, siendo positiva en 11; 38 fueron clasificados como NCC definitiva y 8 probable. Recibieron solamente tratamiento sintomático18 pacientes, 27 tratamiento antiparasitario y 6 adicionalmente tratamiento neuroquirúrgico. Falleció un paciente. CONCLUSIONES: La sintomatología y los hallazgos de neuroimágenes fueron proteiformes y la mortalidad fue baja.

BACKGROUND: Neurocysticercosis (NCC) is the most common parasitosis of the central nervous system, and a very important cause of epilepsy. AIM: To describe the clinical features of patients with NCC attending a high level hospital from Lambayeque during: 2016-2018. METHODS: The medical records of patients with NCC were reviewed, and their information was collected on a data sheet. RESULTS: 46 stories met the inclusion criteria; 23 patients were male, the median age was 46.5 years (IQR: 26.5-63), the youngest patient was 7 years old, and the longest 85. Thirty patients were from Lambayeque. Epilepsy occurred in 24 patients, intracranial hypertension in 10, psychic syndrome in 2 and focal neurological deficit and visual syndrome in 1; there was one asymptomatic patient and seven had epilepsy and another syndrome. In neuroimaging, cerebral calcifications were the most common lesions; 9 patients had subarachnoid cysts. Serology (western blot) was performed in 20 patients being positive in 11; 38 were definitive NCC and 8 probable. Eighteen patients received only symptomatic treatment, 27 antiparasitic treatment and 6, additionally neurosurgical treatment. Only one patient died. CONCLUSIONS: The symptoms and neuroimaging findings were proteiform and the mortality found was low.