RESUMEN
On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.
Asunto(s)
Antineoplásicos/uso terapéutico , Carbolinas/uso terapéutico , Aprobación de Drogas , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carbolinas/farmacología , Terapia Combinada , Manejo de la Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Retratamiento , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Resultado del Tratamiento , Estados Unidos , United States Food and Drug AdministrationAsunto(s)
Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Aprobación de Drogas , Mieloma Múltiple/tratamiento farmacológico , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Químicos , Complejo de la Endopetidasa Proteasomal/metabolismo , Factores de Tiempo , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Toxicological studies constitute an essential part of the effort in developing a botanical supplement into a drug product. The US Food and Drug Administration recently published a draft guidance and established a special botanical review team to assist academic and industry sponsors to manage this and other regulatory considerations related to this unique group of drug products. In this article, the current state of regulatory viewpoints on issues related to requirements and recommendations of various types of nonclinical toxicity studies in support of advanced phases clinical trials and filing a New Drug Application of a botanical are discussed. Topics include nonclinical pharmacology/toxicology view of previous human experience and initial clinical trial, regulatory perspectives on acute toxicity studies, chronic toxicity studies, mutagenicity studies, reproductive toxicity studies, and carcinogenicity studies on botanicals. Certain regulatory review-related issues are also presented. It is anticipated that through a proactive 2-way communication between the Agency and the sponsor, toxicological development of botanical drug product can be significantly facilitated.
