Oliver Gautschi1, Sacha I Rothschild2, Qiyu Li3, Klazien Matter-Walstra4, Alfred Zippelius2, Daniel C Betticher5, Martin Früh6, Rolf A Stahel7, Richard Cathomas8, Daniel Rauch9, Miklos Pless10, Solange Peters11, Patrizia Froesch12, Thilo Zander13, Martina Schneider3, Christine Biaggi3, Nicolas Mach14, Adrian F Ochsenbein15. 1. Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland. Electronic address: oliver.gautschi@luks.ch. 2. Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. 3. Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland. 4. Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland; Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland. 5. Department of Medical Oncology, Cantonal Hospital Fribourg, Fribourg, Switzerland. 6. Department of Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland. 7. Department of Medical Oncology, University Hospital Zurich, Zurich, Switzerland. 8. Department of Medical Oncology, Cantonal Hospital Graubünden, Chur, Switzerland. 9. Oncology Center, Hospital Simmental-Thun-Saanenland AG, Thun, Switzerland. 10. Tumor Center, Cantonal Hospital Winterthur, Winterthur, Switzerland. 11. University Hospital Lausanne, Cancer Center, Lausanne, Switzerland. 12. Istituto Oncologico Svizzera Italiana, Bellinzona, Switzerland. 13. Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland. 14. Department of Medical Oncology, University Hospital Geneva, Geneva, Switzerland. 15. Department of Medical Oncology, University Hospital Bern, Bern, Switzerland.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.