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
Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland.
Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Clin Lung Cancer. 2017 May;18(3):303-309. doi: 10.1016/j.cllc.2016.11.007. Epub 2016 Nov 23.
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.
培美曲塞和贝伐单抗作为单药已被批准用于晚期非鳞状非小细胞肺癌患者铂类诱导化疗后的维持治疗。目前尚不清楚贝伐单抗联合培美曲塞是否优于单用培美曲塞。
我们进行了一项非随机的II期试验，有2个连续队列。在第一个队列中，77例患者每3周接受4个周期的顺铂、贝伐单抗和培美曲塞治疗，随后接受贝伐单抗联合培美曲塞维持治疗直至疾病进展。在第二个队列中，我们对52例未使用贝伐单抗的患者单用培美曲塞进行维持治疗。比较了两个队列的无进展生存期（PFS）、总生存期（OS）、总缓解率（ORR）、不良事件和治疗费用。
从登记时起，队列1的中位PFS为6.9个月，队列2为5.6个月。队列1的ORR为62.3%，队列2为44.2%。队列1的PFS（风险比，0.7；95%置信区间[CI]，0.5 - 1.0；P = .041）和ORR（优势比，2.1；95%CI，1.0 - 4.3；P = .049）优于队列2。在对队列1进行47个月的中位随访期和对队列2进行27个月的中位随访期后，未发现OS有差异（风险比，1.0；95%CI，0.7 - 1.6；P = .890）。队列1中≥3级不良事件的发生率更高。队列1中每位患者的治疗费用平均高出1.4倍。
在我们的非随机试验中，添加贝伐单抗增加了ORR和PFS，但未增加OS。此外，添加贝伐单抗与更高的毒性和更高的费用相关。
