ABSTRACT
BACKGROUND: ARCHER 1050, an ongoing, randomized, open-label, phase III trial of dacomitinib versus gefitinib in newly diagnosed patients with advanced non-small-cell lung cancer (NSCLC) and an EGFR-activating mutation, reported significant improvement in overall survival (OS) with dacomitinib. OBJECTIVE: This paper reports an updated OS analysis of ARCHER 1050 after an extended follow-up. PATIENTS AND METHODS: In this multinational, multicenter trial, adults (aged ≥ 18 years or ≥ 20 years in Japan and Korea) with newly diagnosed NSCLC and EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and no history of central nervous system metastases, were randomized 1:1 to receive dacomitinib 45 mg/day (n = 227) or gefitinib 250 mg/day (n = 225). Randomization was stratified by race and EGFR mutation type. An ad hoc updated analysis of OS was conducted at the protocol-defined cut-off of 48 months from first dosing of the last enrolled patient (13 May 2019). RESULTS: After a median follow-up of 47.9 months, 133 (58.6%) patients had died in the dacomitinib arm and 152 (67.6%) in the gefitinib arm. The hazard ratio (HR) for OS was 0.748 (95% CI 0.591-0.947; two-sided P = 0.0155); median OS was 34.1 months with dacomitinib versus 27.0 months with gefitinib. The HR for OS in patients with dose reduction(s) in the dacomitinib arm (n = 154) compared with all patients in the gefitinib arm was 0.554 (95% CI 0.420-0.730); median OS was 42.5 months for patients with dose reduction(s) in the dacomitinib arm. The most common adverse events were diarrhea (87.7%), paronychia (61.7%), dermatitis acneiform (49.3%), and stomatitis (43.6%) with dacomitinib, and diarrhea (55.8%) and alanine aminotransferase increased (40.2%) with gefitinib. CONCLUSIONS: The OS benefit from first-line treatment with dacomitinib versus gefitinib was maintained after extended follow-up in patients with advanced NSCLC with EGFR-activating mutations. CLINICALTRIALS.GOV: NCT01774721 (registered 24 January 2013).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Gefitinib/pharmacology , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Quinazolinones/pharmacology , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/metabolism , Dose-Response Relationship, Drug , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Gefitinib/administration & dosage , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Male , Mutation , Protein Kinase Inhibitors/administration & dosage , Quinazolinones/administration & dosage , Survival AnalysisABSTRACT
BACKGROUND: The number of patients with diabetes is growing worldwide. In particular this increase, most pronounced for type 2 diabetes, affects South-Asians. In Norway pregnant women originating from this region are more prone to gestational diabetes than ethnic Norwegians. More knowledge is needed to prevent and treat this disease effectively. Here we give a brief overview of the epidemiology and risk factors associated with gestational diabetes. MATERIALS AND METHODS: Information related to gestational diabetes was obtained from various databases, including PubMed, HighWire and Ovid, in addition to our own experience. RESULTS AND INTERPRETATION: Some methodological aspects preclude a definite assessment of the true extent of gestational diabetes nationally as well as internationally. About 0.01 3% of Caucasian pregnancies are affected while the corresponding number among South-Asian women is 5 to 10 times higher. Most studies identify obesity as an important risk factor. Generally, advice on diet and physical activity can prevent diabetes. Similar interventions might also be useful among the increasing population of immigrant fertile women in Norway.
