title: Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).
abstract: Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; P<0.001) and response (P=0.032). This review confirms the poorer outcomes in PS2 vs. PS0-1 patients. Although it is not an approved combination therapy, in clinical studies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.
authors.affiliation: Departments of Investigational Cancer Therapeutics, and Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Zinner
authors.affiliation: EU Lead, Late Phase Development, Lilly Oncology, Lilly Nederland B.V., 3991 RA Houten, The Netherlands.
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
mesh_terms: D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D000068437:Pemetrexed / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D016190:Carboplatin