Christopoulos Petros, Prawitz Thibaud, Hong Jin-Liern, Lin Huamao M, Hernandez Luis, Jin Shu, Tan Min, Proskorovsky Irina, Lin Jianchang, Zhang Pingkuan, Patel Jyoti D, Ou Sai-Hong I, Thomas Michael, Stenzinger Albrecht
Thoraxklinik and National Center for Tumor Diseases at Heidelberg University Hospital, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Germany.
Evidera, Inc., Paris, France.
Lung Cancer. 2023 May;179:107191. doi: 10.1016/j.lungcan.2023.107191. Epub 2023 Apr 8.
Mobocertinib, a novel oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is available for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations after platinum chemotherapy. We performed an indirect comparison of clinical trial data and real-world data (RWD) to determine the relative efficacy of mobocertinib vs. other treatments for these patients.
Data on the efficacy of mobocertinib from a phase I/II trial (NCT02716116) were compared to RWD from a retrospective study in 12 German centers using inverse probability of treatment weighting to adjust for age, sex, Eastern Cooperative Oncology Group score, smoking status, presence of brain metastasis, time from advanced diagnosis, and histology. Tumor response assessment was based on RECIST v1.1.
The analysis included 114 patients in the mobocertinib group and 43 in the RWD group. The confirmed overall response rate (cORR) according to investigator assessment was 0% for standard treatments and 35.1% (95% confidence interval [CI], 26.4-44.6) for mobocertinib (p < 0.0001). Compared to standard regimens in the weighted population, mobocertinib prolonged overall survival (OS, median [95% CI] = 9.8 [4.3-13.7] vs. 20.2 [14.9-25.3] months; hazard ratio [HR] = 0.42 [0.25-0.69], p = 0.0035), progression-free survival (PFS, median [95% CI] = 2.6 [1.5-5.7] vs. 7.3 [5.6-8.8] months; HR = 0.28 [0.18-0.44], p < 0.0001), and time to treatment discontinuation (median [95% CI] = 2.1 [1.2-3.1] vs. 7.4 [6.4-8.5] months; HR = 0.34 [0.18-0.65], p = 0.0004).
Mobocertinib was associated with an improved cORR and prolonged PFS and OS compared to standard treatments for patients with EGFR ex20ins-positive NSCLC previously treated with platinum-based chemotherapy.
莫博替尼是一种新型口服表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，可用于治疗铂类化疗后出现EGFR外显子20插入（ex20ins）突变的非小细胞肺癌（NSCLC）。我们对临床试验数据和真实世界数据（RWD）进行了间接比较，以确定莫博替尼与其他治疗方法对这些患者的相对疗效。
将一项I/II期试验（NCT02716116）中莫博替尼的疗效数据与德国12个中心的一项回顾性研究中的RWD进行比较，使用治疗权重的逆概率来调整年龄、性别、东部肿瘤协作组评分、吸烟状况、脑转移的存在、晚期诊断后的时间和组织学。肿瘤反应评估基于RECIST v1.1。
分析包括莫博替尼组的114例患者和RWD组的43例患者。根据研究者评估，标准治疗的确认总缓解率（cORR）为0%，莫博替尼为35.1%（95%置信区间[CI]，26.4 - 44.6）（p < 0.0001）。与加权人群中的标准治疗方案相比，莫博替尼延长了总生存期（OS，中位数[95%CI] = 9.8 [4.3 - 13.7] 个月 vs. 20.2 [14.9 - 25.3] 个月；风险比[HR] = 0.42 [0.25 - 0.69]，p = 0.0035）、无进展生存期（PFS，中位数[95%CI] = 2.6 [1.5 - 5.7] 个月 vs. 7.3 [5.6 - 8.8] 个月；HR = 0.28 [0.18 - 0.44]，p < 0.0001）和治疗中断时间（中位数[95%CI] = 2.1 [1.2 - 3.1] 个月 vs. 7.4 [6.4 - 8.5] 个月；HR = 0.34 [0.18 - 0.65]，p = 0.0004）。
与先前接受铂类化疗的EGFR ex20ins阳性NSCLC患者的标准治疗相比，莫博替尼与改善的cORR以及延长的PFS和OS相关。
