Comprehensive Cancer Center Munich & Department of Medicine III, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Department of Medicine I, University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
BMC Cancer. 2020 Feb 24;20(1):155. doi: 10.1186/s12885-020-6636-7.
Gemcitabine/erlotinib treatment offers limited benefit in unselected patients with pancreatic ductal adenocarcinoma (PDAC). Development of skin rash has been associated with favorable outcomes in patients treated with gemcitabine/erlotinib. This study aimed to extend knowledge on the effectiveness of gemcitabine/erlotinib in metastatic PDAC in the context of clinical practice and with focus on skin rash.
This multicenter, non-interventional study enrolled 376 patients with metastatic PDAC receiving gemcitabine/erlotinib. The primary endpoint was overall survival (OS) in patients with skin rash versus no skin rash. Secondary endpoints included progression-free survival (PFS), treatment satisfaction and safety. All data were analyzed using descriptive statistics. Survival time and time to disease progression were estimated using the Kaplan-Meier method. Effectiveness endpoints were analyzed for subgroups by skin rash grade (no rash, rash grade 1, rash grade ≥ 2), duration of erlotinib treatment (≤8 weeks, > 8 weeks), Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0-1, 2) and age (≤65 years, > 65 years).
Within the full analysis set (FAS; N = 270), 48 patients (17.8%) developed grade 1 rash, 51 patients (18.9%) grade ≥ 2 rash, while 171 patients (63.3%) did not develop a rash. Median OS of all patients was 9.11 months with an OS of 9.93 months in rash-positive and 8.68 months in rash-negative patients. Median PFS was 5.06 months for rash-positive and 4.11 months for rash-negative patients. PFS was longer in patients with rash grade ≥ 2 and in older patients (> 65 years). Examination using a multivariate Cox proportional model revealed that an age > 65 years was associated with longer OS (hazard ratio 0.640; p = 0.0327) and PFS (hazard ratio 0.642; p = 0.0026). Out of the 338 patients in the SAF, 310 patients (91.7%) experienced at least one AE, and 176 patients (52.1%) experienced skin-related side effects, all of which were CTC grade 1 to 3.
Comparing rash-positive with rash-negative patients showed no significant difference in survival. While patients with rash grade ≥ 2 and older patients (independent of skin reactions) showed longer PFS, this did not translate into prolonged OS. The study did not reveal new safety signals.
ClinicalTrials.gov Identifier: NCT01782690, retrospectively registered on 4 February 2013.
吉西他滨/厄洛替尼治疗在未选择的胰腺导管腺癌（PDAC）患者中获益有限。皮疹的发生与接受吉西他滨/厄洛替尼治疗的患者的良好结局相关。本研究旨在扩展吉西他滨/厄洛替尼在转移性 PDAC 中的有效性的知识，同时关注皮疹。
这项多中心、非干预性研究纳入了 376 名接受吉西他滨/厄洛替尼治疗的转移性 PDAC 患者。主要终点是皮疹患者与无皮疹患者的总生存期（OS）。次要终点包括无进展生存期（PFS）、治疗满意度和安全性。所有数据均采用描述性统计进行分析。使用 Kaplan-Meier 方法估计生存时间和疾病进展时间。根据皮疹分级（无皮疹、皮疹 1 级、皮疹≥2 级）、厄洛替尼治疗持续时间（≤8 周、>8 周）、基线东部合作肿瘤学组（ECOG）表现状态（0-1、2）和年龄（≤65 岁、>65 岁）对有效性终点进行亚组分析。
在全分析集（FAS；N=270）中，48 名患者（17.8%）出现 1 级皮疹，51 名患者（18.9%）出现≥2 级皮疹，而 171 名患者（63.3%）未出现皮疹。所有患者的中位 OS 为 9.11 个月，皮疹阳性患者的 OS 为 9.93 个月，皮疹阴性患者的 OS 为 8.68 个月。皮疹阳性患者的中位 PFS 为 5.06 个月，皮疹阴性患者的中位 PFS 为 4.11 个月。皮疹分级≥2 级和年龄较大（>65 岁）的患者 PFS 更长。使用多变量 Cox 比例模型的检查表明，年龄>65 岁与更长的 OS（风险比 0.640；p=0.0327）和 PFS（风险比 0.642；p=0.0026）相关。在 SAF 中的 338 名患者中，310 名患者（91.7%）至少经历了一次 AE，176 名患者（52.1%）经历了皮肤相关的副作用，所有这些副作用均为 CTC 1 级至 3 级。
比较皮疹阳性与皮疹阴性患者，生存无显著差异。虽然皮疹分级≥2 级和年龄较大（无论皮肤反应如何）的患者 PFS 较长，但这并未转化为更长的 OS。该研究未发现新的安全性信号。
ClinicalTrials.gov 标识符：NCT01782690，于 2013 年 2 月 4 日回顾性注册。
