136 research outputs found
Abstract C100: Safety run-in results from phase 3 study of canakinumab (CAN) or placebo in combination with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC (CANOPY-1)
No full textAbstract Cytokine interleukin-1β (IL-1β) has multiple pro-tumorogenic effects on tumor microenvironment, thereby promoting carcinogenesis, tumor invasiveness, and immunosuppression. CAN is a selective IL-1β inhibitor that aims to target tumor-promoting inflammation to reduce immune suppression, thereby potentiating effects of immunotherapy with PD-1 inhibitors such as PEM. Results of phase 3 CANTOS study have shown that IL-1β inhibition with CAN was associated with reduced incidence of lung cancer and lung cancer mortality, thus providing a rationale to investigate therapeutic role of CAN in lung cancer. CANOPY-1 (NCT03631199) is a placebo-controlled, double-blind, randomized, phase 3 trial designed to evaluate efficacy and safety of PEM + Ctx ± CAN in previously untreated pts with stage IIIB/IIIC (not eligible for definitive chemo-radiation curative tx) or stage IV squamous and nonsquamous NSCLC. The study was divided into 2 parts: part 1 is non-randomized, safety run-in part where pts received CAN 200 mg s.c Q3W + PEM 200 mg i.v Q3W + platinum-based Ctx [Cohort A (non-squamous), carboplatin + pemetrexed; Cohort B (non-squamous), cisplatin + pemetrexed; Cohort C (squamous or non-squamous), carboplatin + paclitaxel]. Part 2 of the study randomizes pts to evaluate efficacy and safety of CAN combination regimen vs placebo combination regimen. Primary objective of safety run-in part: RP3R for CAN in combination with PEM + Ctx. Secondary objectives: ORR, DCR, DOR, safety, PK, and immunogenicity. As of 14 May 2019 (follow-up of ≥42 days from C1D1 unless pt discontinued earlier), 10 pts in cohort A (A), 11 pts in cohort B (B), and 9 pts in cohort C (C) were treated, of which 73% were male, median age was 63 yrs. In total, 24/30 (80%) pts enrolled were still receiving tx; primary reason for tx discontinuation was progressive disease (5 pts; 3 pts in A and 1 pt each in B and C) and 1 patient died due to study indication. Dose-limiting toxicity (DLT) occurring during first 42 days of study tx was reported only in 1 pt (cohort C: grade 3 hepatitis, not related to CAN). Recommended phase 3 regimen (RP3R) of CAN in combination with standard dose of PEM + Ctx was confirmed as 200 mg SC Q3W based on Bayesian logistic regression model (BLRM). Serious AEs regardless of study drug relationship were reported in 8 (27%) pts (2 pts in A and 3 pts each in B and C), none of which considered to be related to CAN. Most common AEs (≥20%, any grade) across all cohorts (n=30) were nausea (37%), vomiting (30%), constipation and fatigue (each 23%), and neutrophil count decrease (20%). Overall, 14 pts (47%) experienced grade 3 AEs and 1 pt experienced grade 4 AE (cardiac tamponade unrelated to study drugs). No fatal serious AEs were reported. AEs leading to discontinuation of one of the study drugs were reported in 3 (10%) pts (hepatitis, peripheral neuropathy, and polyneuropathy) but none were CAN related. AEs leading to dose reduction and dose interruption of one of study drugs were reported in 3 (10%) pts and 5 (17%) pts, respectively. Only 1 DLT was reported with this triplet combination of CAN + PEM + Ctx. Based on BLRM and all relevant data, the RP3R of CAN as 200 mg SC Q3W combination was considered safe and well tolerated. Enrolment is ongoing in randomized phase 3 part of study to evaluate efficacy and safety. Citation Format: Bruce E. Johnson, Tae Min Kim, T. Jeroen N. Hiltermann, Fabrice Barlesi, Christian Grohe, Yasushi Goto, Orvar Gunnarsson, Tobias Overbeck, Noemi Reguart, Martin Wermke, Gilberto Castro, Enriqueta Felip, Alastair Greystoke, Benjamin J. Solomon, Noelia Nebot, Stephanie Deudon, Anne-Laure Louveau, Vanessa Q. Passos, Daniel SW Tan. Safety run-in results from phase 3 study of canakinumab (CAN) or placebo in combination with pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) as 1st line therapy in patients (pts) with advanced or metastatic NSCLC (CANOPY-1) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C100. doi:10.1158/1535-7163.TARG-19-C10
Molecular target therapy for bone metastasis: starting a new era with denosumab, a RANKL inhibitor
No full textINTRODUCTION:
The skeleton is generally the primary, and sometimes the only, site of metastasis in patients with advanced solid tumors. Bone metastases are the most frequent cause of cancer-related pain and the origin of severe morbidity in patients. Among the treatment options available for the prevention of skeletal-related events (SREs) associated with bone metastasis, zoledronic acid, an antiresorptive treatment from the group of bisphosphonates, is currently the standard of care in this setting.
AREAS COVERED:
Zoledronic acid, together with denosumab (a monoclonal antibody against the receptor activator of nuclear factor kappa B ligand), is the most frequent approach for the prevention of cancer-related events in skeleton. This paper reviews several trials evaluating the efficacy of denosumab in comparison with zoledronic acid in patients with solid osteotropic tumors. In this setting of skeleton-invading cancers, denosumab was demonstrated to be superior to zoledronic acid in preventing or delaying SREs. In comparison with zoledronic acid, denosumab significantly delayed the time to first SRE by 17%.
EXPERT OPINION:
Current research on denosumab is addressed to prove the immunomodulator effect of this agent in humans. Other avenue of research is focused on its antitumor activity observed in some Phase III trials
Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry
No full textFundacion Mutua Madrilena; Fondo de Investigaciones Sanitarias [PI11/02866]Conde, E., Suárez-Gauthier, A., Benito, A., Garrido, P., García-Campelo, R., Biscuola, M., Paz-Ares, L., Hardisson, D., De Castro, J., Camacho, M.C., Rodriguez-Abreu, D., Abdulkader, I., Ramirez, J., Reguart, N., Salido, M., Pijuán, L., Arriola, E., Sanz, J., Folgueras, V., Villanueva, N., Gómez-Román, J., Hidalgo, M., López-Ríos, F
Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions
No full textLa evolución en el aprendizaje del alumnado a través de la contrapráctica en la asignatura de Derecho Eclesiástico del Estado
No full text[ES] Ante la creciente necesidad de reforzar el proceso de aprendizaje del alumnado, la contrapráctica se proyecta como una herramienta educativa innovadora capaz de conseguir la evolución en dicho aprendizaje. A través de esta actividad, que ya se ha puesto en práctica en la asignatura de Derecho Eclesiástico del Estado por parte del profesorado de la Universitat Jaume I de Castellón, se otorga al alumno la posibilidad de estudiar a fondo un tema de gran actualidad para realizar una reflexión jurídica. Su trabajo autónomo previo se verá complementado y perfeccionado con una exposición jurídico-práctica rigurosamente actualizada por parte del docente tras la que este planteará al estudiantado una práctica experimental con el objetivo de contrastarla con la realidad jurídica. La evolución en el aprendizaje tendrá lugar cuando el alumnado sea capaz de llevar a cabo un análisis de fundamentación fáctico y jurídico, pero enriquecido con el contraste empírico basado en experiencias personales o de terceros que pueda conducir a un debate de gran calado en relación a posibles desajustes entre el derecho y la realidad social.[EN] In view of the growing need to reinforce the students’ learning process, the counterpractice is projected as an innovative educational tool capable of achieving a learning evolution. Through this activity, which has already been implemented in the subject of Ecclesiastical Law of the State at the Jaume I University of Castellón, the student is granted the possibility of studying in depth a highly topical issue to prepare a legal reflection. Their previous autonomous work will be complemented and perfected with a rigorously updated legal-practical exposition by the teacher after which she will propose to the student an experimental practice with the aim of contrasting it with the legal reality. The learning evolution will take place when students are able to carry out an analysis of factual and legal basis, but enriched with the empirical contrast based on personal or third-party experiences that can lead to a major debate in relation to possible mismatches between law and social reality.Reguart Segarra, N.; Camarero Suárez, V. (2021). La evolución en el aprendizaje del alumnado a través de la contrapráctica en la asignatura de Derecho Eclesiástico del Estado. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 61-70. https://doi.org/10.4995/INRED2020.2020.11946OCS617
Safety of tarlatamab with 6-8-h outpatient versus 48-h inpatient monitoring during cycle 1: DeLLphi-300 phase 1 substudy
No full textPatient monitoring; Safety; Small-cell lung cancerMonitoreo de pacientes; Seguridad; Cáncer de pulmón de células pequeñasMonitorització de pacients; Seguretat; Càncer de pulmó de cèl·lules petitesBackground
Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has demonstrated promising survival outcomes in small-cell lung cancer (SCLC). Given the risk of cytokine release syndrome (CRS), initial clinical trials incorporated 48-72-h inpatient monitoring in cycle 1.
Methods
Patients with previously treated SCLC were enrolled into DeLLphi-300 part F, which evaluated the safety of tarlatamab 10 mg every 2 weeks (Q2W) with 6-8-h outpatient monitoring following cycle 1 doses. The primary endpoint, safety, was compared with patients from DeLLphi-300 part A receiving tarlatamab 10 mg Q2W with 48-h inpatient monitoring for cycle 1 doses.
Results
In cycle 1, the rates of treatment-related adverse events and hospitalizations, including emergency room visits, were similar between outpatient (n = 30) and inpatient (n = 58) groups (93% versus 100% and 27% versus 34%, respectively). The incidence of all grade and serious CRS during cycle 1 was similar between outpatient and inpatient groups (any grade: 60% versus 62%; serious: 17% versus 22%). The median time to CRS resolution was 3 days for both groups.
Conclusions
Safety outcomes, including hospitalization rates, were similar in this first-in-human study following tarlatamab 10 mg Q2W administration with 6-8-h outpatient versus 48-h inpatient monitoring in cycle 1.This work was funded by Amgen Inc.; DeLLphi-300 ClinicalTrials.gov number NCT03319940 (no grant number)
De-escalation strategies with targeted therapies in non-small cell lung cancer
No full textTargeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly EGFR-mutant and ALK-rearranged tumors, have become the standard of care across nearly all stages of the disease. However, the arbitrarily defined dose and treatment duration of TT, as well as the financial cost of these drugs, reduce their availability worldwide. Pharmacokinetic and pharmacodynamic properties of TT suggest that doses of some TT are overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. Some academic initiatives have been launched aiming to explore de-escalating strategies with TT, either reducing the dose or the duration of these drugs. These approaches can decrease the risk of adverse events positively impacting patients’ quality of life, without compromising efficacy, while reducing economic impact. In this review, we summarize current data regarding de-escalating strategies with TT, ongoing trials and challenges of this approach
Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆
No full textNo abstract availabl
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