title: Trends in phase III randomized controlled clinical trials on the treatment of advanced non-small-cell lung cancer.
abstract: The objective of this review was to analyze trends in outcomes and in the quality of phase III randomized controlled trials on advanced NSCLC published between 2000 and 2012, selecting 76 trials from a total of 122 retrieved in a structured search. Over the study period, the number of randomized patients per trial increased by 14 per year (P = 0.178). The sample size significantly increased between 2000 and 2012 in trials of targeted agents (460.1 vs. 740.8 patients, P = 0.009), trials of >1 drug (360.4 vs. 584.8, P = 0.014), and those including patients with good performance status (675.3 vs. 425.6; P = 0.003). Quality of life was assessed in 46 trials (60.5%), and significant improvements were reported in 10 of these (21.7%). Platinum-based regimens were the most frequently investigated (86.8% of trials). Molecular-targeted agents were studied in 25.0% of chemotherapy arms, and the percentage of trials including these agents increased each year. The median (interquartile range) overall survival (MOS) was 9.90 (3.5) months with an increase of 0.384 months per year of publication (P < 0.001). A statistically significant improvement in MOS was obtained in only 13 (18.8%) trials. The median progression-free survival was 4.9 (1.9) months, with a nonsignificant increase of 0.026 months per year (P > 0.05). There has been a continuous but modest improvement in the survival of patients with advanced NSCLC over the past 12 years. Nevertheless, the quality of clinical trials and the benefit in outcomes should be carefully considered before the incorporation of novel approaches into clinical practice.
authors.affiliation: Department of Pharmacy, Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada/University of Granada, Granada, Spain. cristinafernandez85@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-López
authors.affiliation: Department of Oncology, Virgen de las Nieves Universitary Hospital, Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Expósito-Hernández
authors.affiliation: Department of Oncology, Virgen de las Nieves Universitary Hospital, Granada, Spain.
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Arrebola-Moreno
authors.affiliation: Department of Pharmacy, Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada/University of Granada, Granada, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Calleja-Hernández
authors.affiliation: Unit Research Support, Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada/University of Granada, Granada, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Expósito-Ruíz
authors.affiliation: Department of Oncology, Virgen de las Nieves Universitary Hospital, Granada, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerrero-Tejada
authors.affiliation: Department of Oncology, Virgen de las Nieves Universitary Hospital, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Linares
authors.affiliation: Department of Pharmacy, Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada/University of Granada, Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cabeza-Barrera
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D009026:Mortality; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
keywords: Advanced stage; non-small-cell lung cancer; randomized controlled trial; review; treatment