Spira Alexander I, Paz-Ares Luis, Han Ji-Youn, Shih Jin-Yuan, Mascaux Céline, Roy Upal Basu, Zugazagoitia Jon, Kim Yu Jung, Chiu Chao-Hua, Kim Sang-We, Nadal Ernest, Gil-Bazo Ignacio, Murphy Sean P, Anderson Bailey G, Xia Yichuan, Wang George, Bauml Joshua M, Chioda Marc, Simoes Jairo, Mahadevia Parthiv J, Lopes Gilberto
Virginia Cancer Specialists, Fairfax, Virginia.
Hospital Universitario 12 de Octubre, Madrid, Spain.
J Thorac Oncol. 2025 Jun;20(6):809-816. doi: 10.1016/j.jtho.2025.01.018. Epub 2025 Jan 24.
Amivantamab, an EGFR-MET bispecific antibody, is approved for multiple indications in EGFR-mutated advanced NSCLC as monotherapy or combined with other agents. Intravenous amivantamab is associated with a 67% infusion-related reaction (IRR) rate.
The phase 2 SKIPPirr study (NCT05663866) enrolled participants with EGFR-mutated (exon 19 deletion or exon 21 L858R) advanced NSCLC after progression on osimertinib and platinum-based chemotherapy who received intravenous amivantamab plus oral lazertinib (amivantamab-lazertinib), a third-generation tyrosine kinase inhibitor. Aiming to mitigate IRRs, four independent prophylactic approaches were evaluated using Simon's two-stage design with an expansion stage if a cohort passed both stages: oral dexamethasone 4 mg twice daily given on cycle (C) 1 day (D) -1 (two doses); oral dexamethasone 8 mg twice daily given on C1D-2, C1D-1, and the morning of C1D1 (five doses); oral montelukast 10 mg once daily given on C1D-4, C1D-3, C1D-2, C1D-1, and C1D1 (five doses); subcutaneous methotrexate 25 mg (one dose) given anytime between C1D-7 and C1D-3. The primary end point was C1D1 IRR incidence.
As of June 24, 2024, 68 participants were treated across all cohorts. The dexamethasone 8 mg cohort passed stages 1 and 2 proceeding to the expansion stage, with 24 additional participants treated. At C1D1, nine of 40 participants (22.5%) experienced IRRs, resulting in an approximately threefold decrease versus historical data (67.4%). By the end of C3, 10 of 41 participants (24.4%) in the dexamethasone 8 mg cohort experienced IRRs (grades 1-2, except one grade 3 on C2D1). Amivantamab-lazertinib's safety and efficacy were consistent with previous reports.
Prophylaxis with 8 mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.
阿米万他单抗是一种表皮生长因子受体-间质表皮转化因子（EGFR-MET）双特异性抗体，已被批准用于表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的多种适应症，可单药治疗或与其他药物联合使用。静脉注射阿米万他单抗的输液相关反应（IRR）发生率为67%。
2期SKIPPirr研究（NCT05663866）纳入了在奥希替尼和铂类化疗进展后，携带EGFR突变（外显子19缺失或外显子21 L858R）的晚期NSCLC患者，这些患者接受静脉注射阿米万他单抗加口服拉泽替尼（阿米万他单抗-拉泽替尼），后者是一种第三代酪氨酸激酶抑制剂。为了减轻输液相关反应，采用西蒙两阶段设计评估了四种独立的预防方法，如果一个队列通过两个阶段则进入扩展阶段：在第1周期第-1天（D-1）每日两次口服4毫克地塞米松（两剂）；在第1周期第-2天、第-1天和第1周期第1天上午每日两次口服8毫克地塞米松（五剂）；在第1周期第-4天、第-3天、第-2天、第-1天和第1周期第1天每日一次口服10毫克孟鲁司特（五剂）；在第1周期第-7天至第-3天之间的任何时间皮下注射25毫克甲氨蝶呤（一剂）。主要终点是第1周期第1天的输液相关反应发生率。
截至2024年6月24日，所有队列共有68名参与者接受了治疗。每日两次口服8毫克地塞米松的队列通过了第1阶段和第2阶段，进入扩展阶段，又有24名参与者接受了治疗。在第1周期第1天，40名参与者中有9名（22.5%）出现输液相关反应，与历史数据（67.4%）相比下降了约三倍。到第3周期结束时，每日两次口服8毫克地塞米松队列的41名参与者中有10名（24.4%）出现输液相关反应（1-2级，第2周期第1天有1例3级）。阿米万他单抗-拉泽替尼的安全性和疗效与之前的报告一致。
每日两次口服8毫克地塞米松进行预防可显著降低输液相关反应，且易于在临床实践中实施。
