RESUMEN
INTRODUCTION/BACKGROUND: Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab. MATERIALS AND METHODS: This retrospective study included patients who were initiated on durvalumab for unresectable stage III NSCLC from February 2018 through November 2019. The data analysis utilized descriptive statistics to determine the incidence of pneumonitis associated with durvalumab. RESULTS: Of the 83 patients who were evaluated, 21 patients (25.3%) experienced pneumonitis, with 5 cases (6%) being grade 3/4. Seven patients were re-challenged with durvalumab, while 14 patients permanently discontinued durvalumab. There were no clearly identifiable risk factors leading to an increased incidence of pneumonitis. CONCLUSION: The results of this study indicate that real-world incidence of pneumonitis in stage III NSCLC patients receiving durvalumab consolidation therapy is congruent with the incidence reported in the PACIFIC trial.
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Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Neumonía/inducido químicamente , Neumonía/epidemiología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Estudios Retrospectivos , Medición de RiesgoRESUMEN
OBJECTIVE: The aim of this work was to analyze chemotherapy treatment patterns in patients with advanced breast cancer who had been previously exposed to an anthracycline, a taxane, and capecitabine. METHODS: This retrospective cohort study used medical and pharmacy administrative claims with health-plan enrollment data and medical-record review from a large, US-based health insurer database, the HealthCore Integrated Research Database. Women were included if they were aged > or =18 years at the initial breast cancer diagnosis between January 1999 and July 2005 and had received all 3 drug classes of interest, as well as an initial diagnosis of American Joint Committee on Cancer stage I to III breast cancer with metastatic recurrence or an initial diagnosis of stage IV disease. Information about demographics, clinical and pathologic characteristics, survival, and treatments were obtained from computerized data and medical record review. Descriptive analyses were conducted to characterize the treatment patterns. RESULTS: One hundred forty-four women with advanced breast cancer were identified. Patients ranged in age from 28 to 76 years, with a mean (SD) age of 48.2 (9.1) years, and with 54 patients (37.5%) aged 40 to 49 years and 48 patients (33.3%) aged 50 to 59 years at the time of initial diagnosis. Ninety-three patients (64.6%) were white, 15 (10.4%) were black, 7 (4.9%) were Hispanic, and 4 (2.8%) were Asian. Overall, 89 patients (61.8%) received > or =1 additional chemotherapy regimen after exposure to all 3 chemotherapy agents of interest; 55 (38.2%) received > or =2 additional regimens. A variety of chemotherapeutic regimens were prescribed; 14 monotherapy regimens and 37 combination therapy regimens were used. The most common regimens (both as single agents and combination therapy) included gemcitabine, vinorelbine, or retreatment with a taxane. Of the 89 patients who received > or =1 retreatment, 7 (7.9%) were retreated with anthracycline, 12 (13.5%) with a taxane, and 9 (10.1%) with capecitabine. For first and second treatment after exposure to all 3 agents of interest, the most common single-agent regimens were gemcitabine (first: 17 patients [19.1%]; second: 9 patients [16.4%]) and vinorelbine (first: 14 patients [15.7%]; second: 9 patients [16.4%]). The most common combination therapies for first retreatment were carboplatin based (6 patients [6.7%]). CONCLUSIONS: Of these patients with advanced breast cancer, 61.8% received > or =1 additional chemotherapy regimen after previous treatment with an anthracycline, a taxane, and capecitabine. The variety of agents prescribed suggests a lack of standard of care. Rigorous clinical effectiveness studies of common regimens in heavily pretreated and chemotherapy-resistant populations with breast cancer are warranted.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Pautas de la Práctica en Medicina/normas , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Retratamiento , Estudios Retrospectivos , Sobrevida , Resultado del TratamientoRESUMEN
Pancreatic carcinoma is an unusually lethal disease and to date treatment with standard chemotherapy has yielded disappointing results. The epidermal growth factor receptor (EGFR) is known to be over-expressed in pancreatic cancer and there is data to suggest that this molecular characteristic may be a poor prognostic factor as it may denote a more aggressive form of the disease. Current therapeutic modalities to target the EGFR include monoclonal antibodies directed against the extracellular domain of the receptor as well as tyrosine kinase inhibitors that disable the activating portion of the receptor. Preclinical studies in pancreatic cancer models have demonstrated the efficacy of both of these treatment options and at present they are in various stages of clinical testing in combination with other cytotoxic drugs, with other biologic therapies and in conjunction with radiotherapy. The combination of gemcitabine and one of the tyrosine kinase inhibitors, erlotinib, is the first combination therapy to demonstrate survival benefits in pancreatic cancer in a phase III study albeit a modest one. Increased understanding of the EGFR pathway may permit the use of other targeted agents to either augment therapeutic efficacy or circumvent resistance. Additional EGFR targeted strategies for pancreatic cancer are being developed that may further circumvent mechanisms resistance to EGFR inhibition.
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Antineoplásicos/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pancreáticas/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Receptores ErbB/fisiología , Humanos , Neoplasias Pancreáticas/fisiopatología , Neoplasias Pancreáticas/radioterapia , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Radioterapia Adyuvante , Receptor ErbB-2/fisiologíaRESUMEN
Panitumumab (formerly known as ABX-EGF) is the first fully human monoclonal antibody to epidermal growth factor receptor to enter clinical trials for the treatment of solid tumors. Like cetuximab (Erbitux; BMS), it is directed against the extracellular ligand-binding domain of the receptor and results in blockade of the essential downstream signaling pathways that are known to govern apoptosis, proliferation and differentiation of both normal and neoplastic cell types in a wide array of tissues. It has a very high affinity for epidermal growth factor receptor and has been generally well tolerated and associated with very few infusion reactions. As a fully human agent, panitumumab has not been associated with the formation of any antibodies directed against it that has been evidenced by a very reliable pharmacokinetic profile with possible dosing schedules ranging from 1 to 3 weeks. Similar to other agents targeting the epidermal growth factor receptor pathway, a rash has been the primary toxicity and is dose dependent up to 2.5 mg/kg at which dose 100% of all patients have been affected. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal. It has been efficacious and well tolerated both as monotherapy and in combination with other chemotherapeutic agents. Several phase I trials, two phase II trials and most recently a phase III trial in pretreated colorectal cancer have been carried out to date. Currently, there is also a randomized phase III trial (Panitumumab Advanced Colorectal Cancer Evaluation Study) investigating the role of panitumumab in the first-line treatment of colorectal cancer. No unfavorable drug-drug interactions have been observed nor has there been any effect on the pharmacokinetics of drugs with which it is being used. Recent progress in preclinical and clinical studies of panitumumab is reviewed.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Antineoplásicos/farmacocinética , Cetuximab , Ensayos Clínicos como Asunto , Receptores ErbB/fisiología , Humanos , Tasa de Depuración Metabólica , PanitumumabRESUMEN
Panitumumab (formerly known as ABX-EGF) is the first fully human monoclonal antibody directed against the epidermal growth factor receptor in clinical use. It has proven to be very well tolerated alone and in combination with other cytotoxic chemotherapeutic agents. Panitumumab has demonstrated efficacy as monotherapy and with standard chemotherapeutic agents in a wide variety of cancer types, including non-small-cell lung cancer, renal, and colorectal cancer (CRC). To date, no human antihuman antibodies have been detected, and unlike cetuximab, infusion reactions are infrequent, and no premedications are required when administering panitumumab. The only significant toxicity has been a rash similar to that seen with other agents targeting the epidermal growth factor receptor, and such reactions have been predominantly mild to moderate. In metastatic CRC, panitumumab has been safe and efficacious when given with other commonly used agents in this disease, including irinotecan and fluorouracil. Current studies under way are looking at panitumumab in combination with FOLFOX (fluorouracil/leucovorin/oxaliplatin) plus bevacizumab as well as with novel agents that have yet to come into common clinical practice. Recent progress in development of panitumumab in the management of CRC is reviewed, and management of associated rash is discussed herein.