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

• Published in: Clinical lung cancer 2017-05, Vol.18 (3), p.303-309
• Main Authors: Gautschi, Oliver, Rothschild, Sacha I., Li, Qiyu, Matter-Walstra, Klazien, Zippelius, Alfred, Betticher, Daniel C., Früh, Martin, Stahel, Rolf A., Cathomas, Richard, Rauch, Daniel, Pless, Miklos, Peters, Solange, Froesch, Patrizia, Zander, Thilo, Schneider, Martina, Biaggi, Christine, Mach, Nicolas, Ochsenbein, Adrian F.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - economics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Cohort Studies; Cost-Benefit Analysis; Female; Follow-Up Studies; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Maintenance therapy; Male; Middle Aged; Neoplasm Staging; Pemetrexed; Pemetrexed - therapeutic use; Survival Analysis; Switzerland; Treatment Outcome
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2016.11.007

We previously reported the results of the nonrandomized phase II trial Swiss Group for Clinical Cancer Research (SAKK) 19/09, which studied maintenance therapy with bevacizumab plus pemetrexed in patients with advanced nonsquamous non–small-cell lung cancer. We expanded the trial with a second cohort of patients treated without bevacizumab. The explorative comparison of the 2 cohorts revealed that progression-free survival, but not overall survival, was better with combination maintenance therapy of pemetrexed and bevacizumab. 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.