title: Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer.
abstract: OBJECTIVE
  Single agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear.
  
  
  METHODS
  Chemotherapy-naïve patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate.
  
  
  RESULTS
  One hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6-59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1-51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1-19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7-14.1, hazard ratio: 0.73, 95% CI: 0.44-1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable.
  
  
  CONCLUSIONS
  Both maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan; Department of Clinical Oncology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Karayama
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. Electronic address: inui@hama-med.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Enomoto
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Ensyu Hospital, 1-1-1 Chuou, Hamamatsu 430-0929, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuroishi
authors.affiliation: Department of Respiratory Medicine, Seirei Mikatahara General Hospital, 3453 Mikatahara-cho, Hamamatsu 433-8558, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Yokomura
authors.affiliation: Department of Respiratory Medicine, Fujieda Municipal General Hospital, 4-1-11 Surugadai, Fujieda 426-8677, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koshimizu
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Hamamatsu Hospital, 1088-1 Kobayashi, Hamamatsu 434-8533, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Respiratory Medicine, Hamamatsu Rosai Hospital, 25 Shougen-cho, Hamamatsu, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Toyoshima
authors.affiliation: Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-ando, Shizuoka 420-0881, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Respiratory Medicine, Shizuoka City Shimizu Hospital, 1231 Miyakami, Shizuoka 424-8636, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Respiratory Medicine, Shizuoka City Hospital, 10-93 Ote-cho, Shizuoka 420-8630, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Respiratory Medicine, Iwata City Hospital, 513-2 Ohkubo, Iwata 438-8550, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Imokawa
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin
keywords: Bevacizumab; Carboplatin; Maintenance therapy; Non small cell lung cancer; Pemetrexed