Wang Mengzhao, Xu Yan, Huang Wen-Tsung, Su Wu-Chou, Gao Bo, Lee Chee Khoon, Fang Jian, Zhu Xuehua, Yang Zhenfan, Jänne Pasi A, Yang James Chih-Hsin
Peking Union Medical College Hospital, Beijing, China.
Chi Mei Chest Hospital, Tainan, Taiwan.
Lung Cancer. 2025 Jan;199:108053. doi: 10.1016/j.lungcan.2024.108053. Epub 2024 Dec 2.
Multiple agents can be used to treat patients with EGFR mutated non-small cell lung cancer (NSCLC) who develop resistance to EGFR tyrosine kinase inhibitors (TKIs), but the clinical outcome was not satisfactory, especially in patients with multiple lines of prior therapies. Therefore, there is an unmet medical need for these patients. Sunvozertinib is an oral, potent, irreversible, and mutant-selective EGFR TKI targeting EGFR mutations with weak activity against wild-type EGFR. We investigated the efficacy and safety of sunvozertinib monotherapy in treating EGFR TKI-resistant patients with NSCLC harboring EGFR mutations.
This was a pooled analysis of phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression free survival (PFS). Safety endpoints included adverse events and serious adverse events. In addition, plasma specimens were collected at baseline to assess EGFR mutation types and genetic alterations in EGFR downstream signaling pathway.
Forty patients were enrolled. Ninety percent received ≥ 3 prior lines of therapies. The best ORR was 27.5 %, and DCR was 60 %. The median DoR and PFS were 6.5 months and 6 months, respectively. Higher ORR was seen in patients whose last line of treatment was chemotherapy rather than EGFR TKI (31.6 % vs. 14.3 %). Greater responses were seen in patients with EGFR sensitizing and T790M double mutations (ORR: 55.6 %). The safety profile of sunvozertinib was consistent with previous reports.
Sunvozertinib has promising activity implying future investigations in the patients with EGFR mutated NSCLC who developed resistance to prior EGFR TKI.
多种药物可用于治疗对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）产生耐药的EGFR突变非小细胞肺癌（NSCLC）患者，但临床疗效并不理想，尤其是对于接受过多种前期治疗的患者。因此，这类患者存在未被满足的医疗需求。苏沃替尼是一种口服、强效、不可逆且具有突变选择性的EGFR-TKI，靶向EGFR突变，对野生型EGFR活性较弱。我们研究了苏沃替尼单药治疗携带EGFR突变的EGFR-TKI耐药NSCLC患者的疗效和安全性。
这是一项1期和2期研究（悟空1、悟空2和悟空15）的汇总分析。符合条件的患者接受剂量范围为50mg至400mg的苏沃替尼，每日一次。疗效终点包括客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DoR）和无进展生存期（PFS）。安全性终点包括不良事件和严重不良事件。此外，在基线时采集血浆样本，以评估EGFR突变类型和EGFR下游信号通路的基因改变。
共纳入40例患者。90%的患者接受过≥3线前期治疗。最佳ORR为27.5%，DCR为60%。中位DoR和PFS分别为6.5个月和6个月。最后一线治疗为化疗而非EGFR-TKI的患者ORR更高（31.6%对14.3%）。EGFR敏感和T790M双突变患者的缓解率更高（ORR：55.6%）。苏沃替尼的安全性与既往报道一致。
苏沃替尼具有良好的活性，这意味着未来应对既往EGFR-TKI耐药的EGFR突变NSCLC患者开展进一步研究。
