From the Florida Hospital Cancer Institute, Orlando (M.A.S.); Rocky Mountain Cancer Centers, Denver (R.M.J.); US Oncology, Houston (R.M.J.); Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy (F.C.); Instituto Nacional del Torax, Santiago, Chile (F.O.); Moscow City Oncology Hospital, Moscow (D.S.); National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan (N.N.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain (D.R.-A.); Centre Hospitalier Universitaire de Grenoble Alpes, Grenoble (D.M.-S.), and Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille (F.B.) - both in France; New England Cancer Specialists, Scarborough, ME (C.A.T.); Allegheny Health Network Cancer Institute, Pittsburgh (G.F.); Genentech, South San Francisco, CA (C.K., A.L., S.C., Y.D., Y.S., M.K., A.L.-C., A.S.); and Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.).
N Engl J Med. 2018 Jun 14;378(24):2288-2301. doi: 10.1056/NEJMoa1716948. Epub 2018 Jun 4.
The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy.
We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group.
In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines.
The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann-La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143 .).
阿特珠单抗的杀伤癌细胞的特性可能通过贝伐珠单抗阻断血管内皮生长因子介导的免疫抑制作用得到增强。这项开放标签、3 期研究评估了阿特珠单抗联合贝伐珠单抗联合化疗在未接受过化疗的转移性非鳞状非小细胞肺癌（NSCLC）患者中的应用。
我们随机分配患者接受阿特珠单抗联合卡铂加紫杉醇（ACP）、贝伐珠单抗联合卡铂加紫杉醇（BCP）或阿特珠单抗联合贝伐珠单抗（ABCP），每 3 周治疗 4 或 6 个周期，然后接受阿特珠单抗、贝伐珠单抗或两者维持治疗。两个主要终点是在意向治疗人群中（野生型基因型患者人群；排除 EGFR 或 ALK 基因突变的患者）和在野生型基因（Teff-high WT 人群）患者中肿瘤高表达效应 T 细胞（Teff）基因特征的患者中研究者评估的无进展生存期和总体生存期。在比较 ACP 组与 BCP 组之前，先比较 ABCP 组与 BCP 组。
在野生型基因人群中，356 名患者被分配到 ABCP 组，336 名患者被分配到 BCP 组。与 BCP 组相比，ABCP 组的无进展生存期更长（8.3 个月比 6.8 个月；疾病进展或死亡的风险比为 0.62；95%置信区间[CI]为 0.52 至 0.74；P<0.001）；在 Teff-high WT 人群中，相应的值分别为 11.3 个月和 6.8 个月（风险比为 0.51[95%CI 为 0.38 至 0.68]；P<0.001）。在包括 EGFR 或 ALK 基因突变的患者在内的整个意向治疗人群中，以及在 PD-L1 表达低或阴性、Teff 基因特征低表达和肝转移的患者中，ABCP 组的无进展生存期也长于 BCP 组。野生型基因人群中，ABCP 组的中位总生存期长于 BCP 组（19.2 个月比 14.7 个月；死亡风险比为 0.78；95%CI 为 0.64 至 0.96；P=0.02）。ABCP 的安全性与之前报道的各单药的安全性风险一致。
阿特珠单抗联合贝伐珠单抗加化疗显著改善了转移性非鳞状 NSCLC 患者的无进展生存期和总生存期，无论 PD-L1 表达和 EGFR 或 ALK 基因突变状态如何。（由 F. Hoffmann-La Roche/Genentech 资助；IMpower150 临床试验.gov 编号，NCT02366143）。
