Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata.
ESMO Open. 2024 Apr;9(4):102975. doi: 10.1016/j.esmoop.2024.102975. Epub 2024 Mar 22.
Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM).
Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints.
OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity.
A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.
在两项随机临床试验（SQUIRE 和 JFCM）中已确认尼妥珠单抗[一种阻断配体结合的表皮生长因子受体（EGFR）的人源单克隆抗体]在鳞状（SQ）非小细胞肺癌（NSCLC）患者中的疗效。本研究通过分析两项临床试验（SQUIRE 和 JFCM）的汇总数据，评估了初始皮肤毒性与尼妥珠单抗治疗的疗效之间的关系。
对接受尼妥珠单抗联合吉西他滨和顺铂（N+GC）治疗的 635 例 SQ-NSCLC 患者（意向治疗人群）（SQUIRE 和 JFCM 两项临床试验）的数据进行汇总。评估了第二周期末发生的皮肤毒性与疗效之间的关系。疗效终点包括总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）。对这些终点进行了单变量和多变量分析。
OS 和 ORR 与皮肤毒性相关，而 PFS 则无关。N+GC 组中，与无皮肤毒性（0 级）的患者相比，皮肤毒性≥2 级或 1 级的患者 OS 明显更长[中位值分别为 15.0（≥2 级）、12.7（1 级）、9.4（0 级）个月；风险比（HR）分别为 0.51（≥2 级至 0 级）；95%置信区间（CI）为 0.40-0.64，P<0.001和 HR 分别为 0.64（1 级至 0 级）；95%CI 为 0.52-0.80，P<0.001]。多变量分析显示，OS 与皮肤毒性显著相关。
尼妥珠单抗引起的皮肤毒性与疗效之间存在显著关联。这些结果与先前报道的其他 EGFR 抑制剂引起的皮肤毒性与疗效之间的关联一致。
