PURPOSE Standard first-line therapy for EGFR-mutant advanced non-small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)-directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes. PATIENTS AND METHODS This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity. RESULTS Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively (P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively (P < .001). CONCLUSION Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.

中文翻译：

---

吉非替尼对比吉非替尼加培美曲塞和卡铂化疗治疗 EGFR 突变的肺癌

目的 EGFR 突变晚期非小细胞肺癌 (NSCLC) 的标准一线治疗是表皮生长因子受体 (EGFR) 导向的口服酪氨酸激酶抑制剂。在口服酪氨酸激酶抑制剂中加入培美曲塞和卡铂化疗可能会改善结果。患者和方法 这是一项 III 期随机试验，研究对象为具有 EGFR 致敏突变且体力状态为 0 至 2 分且计划接受一线姑息治疗的晚期 NSCLC 患者。随机分配为 1:1 吉非替尼每天口服 250 mg (Gef) 或吉非替尼每天口服 250 mg 加培美曲塞 500 mg/m2 和卡铂曲线 5 下面积每 3 周静脉注射四个周期，然后维持培美曲塞（吉非替尼加化疗 [Gef+C]）。主要终点是无进展生存期（PFS）；次要终点包括总生存期（OS）、反应率和毒性。结果 2016 年至 2018 年间，350 名患者被随机分配到 Gef（n = 176）和 Gef+C（n = 174）。21% 的患者体力状态为 2，18% 的患者有脑转移。中位随访时间为 17 个月（范围，7 至 30 个月）。Gef+C 组和 Gef 组的放射学反应率分别为 75% 和 63% (P = .01)。Gef+C 的估计中位 PFS 显着长于 Gef（分别为 16 个月 [95% CI，13.5 至 18.5 个月] 和 8 个月 [95% CI，7.0 至 9.0 个月]；疾病进展或死亡的风险比，0.51 [95% CI，0.39 至 0.66]；P < .001）。Gef+C 的估计中位 OS 显着长于 Gef（未达到 v 17 个月 [95% CI，13.5 至 20.5 个月]；死亡风险比，0.45 [95% CI，0. 31 到 0.65]；P < .001)。Gef+C 组和 Gef 组中分别有 51% 和 25% 的患者发生了临床相关的 3 级或更高的毒性（P < .001）。结论 吉非替尼联合培美曲塞和卡铂化疗可显着延长非小细胞肺癌患者的 PFS 和 OS，但增加毒性。