title: Pemetrexed/Carboplatin/Bevacizumab followed by Maintenance Pemetrexed/Bevacizumab in Hispanic Patients with Non-Squamous Non-Small Cell Lung Cancer: Outcomes according to Thymidylate Synthase Expression.
abstract: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
  
  
  
  A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity.
  
  
  
  One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response.
  
  
  
  Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Andrés Felipe
authors.initials: AF
authors.lastname: Cardona
authors.affiliation: Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.|Clinical Oncology Department, Centro Javeriano de Oncología, Hospital Universitario San Ignacio, Bogotá, Colombia.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rojas
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Wills
authors.affiliation: Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Hernán
authors.initials: H
authors.lastname: Carranza
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vargas
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.|Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia.
authors.forename: Jorge
authors.initials: J
authors.lastname: Otero
authors.affiliation: Clinical Oncology Department, Hospital de Clínicas-UdeLAR, Montevideo, Uruguay.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cuello
authors.affiliation: Clinical Oncology Department, Hospital San Juan de Dios, San José, Costa Rica.
authors.forename: Luis
authors.initials: L
authors.lastname: Corrales
authors.affiliation: Thoracic Oncology Unit, Alexander Fleming Institute, Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Martín
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz
authors.affiliation: Clinical and Translational Oncology Group, Thoracic Oncology Unit, Institute of Oncology, Clínica del Country, Bogotá, Colombia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franco
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001706:Biopsy; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage; D011379:Prognosis; D012307:Risk Factors; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin; D013940:Thymidylate Synthase