A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101)
A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101)
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卡铂、培美曲塞和贝伐单抗随后厄洛替尼和贝伐单抗维持治疗野生型 EGFR 非鳞状非小细胞肺癌的 II 期研究 (HOT1101)
DOI：
10.1007/s10147-018-1318-z
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发表时间：
2018
影响因子：
3.3
通讯作者：
Nishimura M
中科院分区：
文献类型：
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作者：
Takashina T;Asahina H;Oizumi S;Yamada N;Harada M;Takamura K;Yokouchi H; Harada T;Honjo O;Ogi T;Morikawa N;Kinoshita I;Honda R;Nakano K;Kanazawa K;Amano T;Dosaka-Akita H;Isobe H;Nishimura M
BackgroundThis study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer（NSCLC）with wild-typeEGFR.MethodsEnrolled patients had treatment-naïve，advanced non-squamous NSCLC with wild-typeEGFR.第1天给予卡铂[曲线下面积（AUC）5.0]、培美曲塞（500 mg/m2）和贝伐珠单抗（15 mg/kg），每3周一次，共4-6个周期。厄洛替尼（150 mg/人）第1天至第21天联合贝伐单抗第1天每3周一次维持治疗，直至疾病进展或出现不可接受的毒性。主要终点为6个月无进展生存期（PFS）;次要终点包括总生存期（OS）、总缓解率（ORR）、毒性反应和生活质量（QOL）。诱导和维持治疗的中位周期数分别为4（范围1-6）和4（范围1-20）。29例患者（58%）接受维持治疗。6个月PFS率为59.5% [95%置信区间（CI）45.0-72.6%]。ORR为48.0%（95% CI 34.8-61.5%），疾病控制率为86.0%（95% CI 73.8-93.0%）。中位PFS和OS分别为6.5个月（95% CI 5.8-7.2个月）和21.4个月（95% CI 15.9-26.9个月）。尽管在33例患者（66.0%）中观察到≥ 3级不良事件，但大多数为血液学不良事件;无发热性中性粒细胞减少症。在整个治疗过程中维持了QOL。结论卡铂/培美曲塞/贝伐珠单抗，随后厄洛替尼和贝伐珠单抗维持治疗在携带野生型EGFR的非鳞状NSCLC患者中显示出适度的疗效，并且耐受性良好。试验注册UMIN 000005872。
BackgroundThis study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-typeEGFR.MethodsEnrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-typeEGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4–6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL).ResultsFifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1–6) and 4 (range 1–20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0–72.6%]. The ORR was 48.0% (95% CI 34.8–61.5%), and disease control rate was 86.0% (95% CI 73.8–93.0%). The median PFS and OS were 6.5 months (95% CI 5.8–7.2 months) and 21.4 months (95% CI 15.9–26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment.ConclusionsCarboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-typeEGFR.Trial registrationUMIN000005872.