Salgia Ravi, Stille John R, Weaver R Waide, McCleod Michael, Hamid Oday, Polzer John, Roberson Stephanie, Flynt Amy, Spigel David R
Department of Medicine, The University of Chicago, Chicago, IL, United States.
Eli Lilly and Company, Indianapolis, IN, United States.
Lung Cancer. 2017 Mar;105:7-13. doi: 10.1016/j.lungcan.2016.12.020. Epub 2016 Dec 31.
This multicenter, open-label, randomized phase II study evaluated the efficacy and safety of LY2510924 (LY) added to first-line standard of care (SOC) chemotherapy for extensive-disease small cell lung cancer (ED-SCLC) and explored the predictive value of C-X-C motif receptor 4 (CXCR4) tumor response.
Patients with treatment-naïve ED-SCLC were randomized (1:1) to receive up to six 21-day cycles of carboplatin/etoposide alone (SOC) or in combination with 20mg LY2510924 administered subcutaneously on days 1-7 of each cycle (LY+SOC). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety. Response relative to CXCR4 expression on baseline tumor was an exploratory endpoint.
Of 94 patients randomized, 90 received treatment (LY+SOC, n=47; SOC, n=43). Median PFS (95% confidence interval [CI]) was 5.88 (4.83, 6.24) months for LY+SOC versus 5.85 (4.63, 5.51) months for SOC (hazard ratio [95% CI], 1.01 [0.62, 1.63]; p=0.9806). Median OS (95% CI) was 9.72 (6.64, 11.70) months for LY+SOC versus 11.14 (8.25, 13.44) months for SOC. ORR was 74.5% for LY+SOC versus 81% for SOC. Safety results between arms were similar, although the following adverse events were more frequent on the LY+SOC arm: anemia (61.7% vs 46.5%), neutropenia (61.7% vs 53.5%), leukopenia (27.7% vs 9.3%), vomiting (27.7% vs 16.3%), and pneumonia (10.6% vs 2.3%). In patients whose baseline CXCR4 expression was above the optimal cutoff (H-score 210), the hazard ratio (95% CI) was 1.27 (0.51, 3.15).
LY2510924 did not improve efficacy but had an acceptable toxicity profile when added to SOC for ED-SCLC.
本多中心、开放标签、随机II期研究评估了在广泛期小细胞肺癌（ED-SCLC）的一线标准治疗（SOC）化疗中加入LY2510924（LY）的疗效和安全性，并探讨了C-X-C基序趋化因子受体4（CXCR4）对肿瘤反应的预测价值。
初治的ED-SCLC患者被随机分组（1:1），接受最多六个21天周期的单纯卡铂/依托泊苷（SOC）治疗，或在每个周期的第1 - 7天皮下注射20mg LY2510924联合卡铂/依托泊苷（LY+SOC）治疗。主要疗效终点为无进展生存期（PFS）。次要终点为总生存期（OS）、总缓解率（ORR）和安全性。相对于基线肿瘤上CXCR4表达的反应是一个探索性终点。
94例随机分组的患者中，90例接受了治疗（LY+SOC组47例；SOC组43例）。LY+SOC组的中位PFS（95%置信区间[CI]）为5.88（4.83，6.24）个月，SOC组为5.85（4.63，5.51）个月（风险比[95%CI]，1.01[0.62，1.63]；p = 0.9806）。LY+SOC组的中位OS（95%CI）为9.72（6.64，11.70）个月，SOC组为11.14（8.25，13.44）个月。LY+SOC组的ORR为74.5%，SOC组为81%。两组间的安全性结果相似，尽管LY+SOC组以下不良事件更常见：贫血（61.7%对46.5%）、中性粒细胞减少（61.7%对53.5%）、白细胞减少（27.7%对9.3%）、呕吐（27.7%对16.3%）和肺炎（10.6%对2.3%）。在基线CXCR4表达高于最佳临界值（H评分210）的患者中，风险比（95%CI）为1.27（0.51，3.15）。
对于ED-SCLC，LY2510924加入SOC治疗时并未提高疗效，但具有可接受的毒性特征。
