title: Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non-Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial.
abstract: Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non-small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.
  
  
  
  We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared.
  
  
  
  The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1.
  
  
  
  The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs.
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland. Electronic address: oliver.gautschi@luks.ch.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Sacha I
authors.initials: SI
authors.lastname: Rothschild
authors.affiliation: Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland; Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland.
authors.forename: Klazien
authors.initials: K
authors.lastname: Matter-Walstra
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Fribourg, Fribourg, Switzerland.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Betticher
authors.affiliation: Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Früh
authors.affiliation: Department of Medical Oncology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Stahel
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Graubünden, Chur, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.affiliation: Oncology Center, Hospital Simmental-Thun-Saanenland AG, Thun, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauch
authors.affiliation: Tumor Center, Cantonal Hospital Winterthur, Winterthur, Switzerland.
authors.forename: Miklos
authors.initials: M
authors.lastname: Pless
authors.affiliation: University Hospital Lausanne, Cancer Center, Lausanne, Switzerland.
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.affiliation: Istituto Oncologico Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Froesch
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland.
authors.forename: Thilo
authors.initials: T
authors.lastname: Zander
authors.affiliation: Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Biaggi
authors.affiliation: Department of Medical Oncology, University Hospital Geneva, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mach
authors.affiliation: Department of Medical Oncology, University Hospital Bern, Bern, Switzerland.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Ochsenbein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000627:therapeutic use*; D016019:Survival Analysis; D013557:Switzerland; D016896:Treatment Outcome
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab
keywords: Bevacizumab; Chemotherapy; Lung cancer; Maintenance therapy; Pemetrexed