Karayama Masato, Inui Naoki, Fujisawa Tomoyuki, Enomoto Noriyuki, Nakamura Yutaro, Kuroishi Shigeki, Yokomura Koshi, Koshimizu Naoki, Sato Masaki, Toyoshima Mikio, Shirai Toshihiro, Masuda Masafumi, Yamada Takashi, Imokawa Shiro, Suda Takafumi
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.
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.
Eur J Cancer. 2016 May;58:30-7. doi: 10.1016/j.ejca.2016.01.013. Epub 2016 Feb 27.
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.
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.
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.
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.
单药维持治疗已被广泛应用于晚期非鳞状非小细胞肺癌（NSCLC）。然而，对于初始和维持阶段的治疗方案尚无共识，且在维持阶段将贝伐单抗添加到细胞毒性药物中的临床获益仍不明确。
未接受过化疗的非鳞状NSCLC患者在接受四个周期的卡铂（曲线下面积=6）、培美曲塞（500mg/m²）和贝伐单抗（15mg/kg）诱导治疗并实现疾病控制后，被随机分配接受培美曲塞联合贝伐单抗或单独使用培美曲塞进行维持治疗。主要终点是1年无进展生存期（PFS）率。
110例患者入组本研究，每组55例。联合维持治疗组的平均1年PFS率为43.9%（95%置信区间[CI]：29.6 - 59.2%），培美曲塞维持治疗组为35.2%（95%CI：22.1 - 51.0%），差异无统计学意义（p = 0.433）。联合维持治疗组从入组开始计算的中位PFS为11.5个月（95%CI：7.1 - 19.0），培美曲塞维持治疗组为7.3个月（95%CI：5.7 - 14.1，风险比：0.73，95%CI：0.44 - 1.19，对数秩检验p = 0.198）。联合维持治疗组鼻出血、高血压和蛋白尿的发生率明显更高，但症状较轻且可耐受。
对于在接受卡铂、培美曲塞和贝伐单抗诱导治疗后实现疾病控制的非鳞状NSCLC患者，单独使用培美曲塞维持治疗以及培美曲塞联合贝伐单抗维持治疗均可行。根据选择设计，未显示这些维持治疗在优越性方面的差异。
