Vietnam National Cancer Hospital, Hanoi, Vietnam.
Bach Mai Hospital, Hanoi, Vietnam.
Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3567-3576. doi: 10.31557/APJCP.2024.25.10.3567.
Afatinib, a second-generation epidermal growth factor receptor(EGFR) tyrosine kinase, has proven effective for non-small-cell lung cancer (NSCLC) patients with EGFR mutations through randomized controlled trials and real-world studies. Elderly patients exhibit unique characteristics in terms of physical condition and comorbidities, leading to differences in clinical practice for selecting the initial dosage and making dose adjustments compared to younger patients. This study aims to evaluate the effectiveness and adverse effects of first-line Afatinib treatment in elderly patients with NSCLC harboring EGFR mutations in Vietnam in a real-world context.
We conducted a retrospective analysis of 135 patients, aged 65 years and older, across nine cancer centers in Vietnam. These patients, who harbored drug-sensitive EGFR mutations (excluding de novo T790M), received first-line Afatinib treatment between April 2018 and June 2022. The primary endpoints, time to treatment failure (TTF), and overall survival (OS) were assessed using the Kaplan-Meier method, and comparisons were conducted using the log-rank test. Secondary endpoints included the overall response rate (ORR) according to RECIST 1.1 and adverse effects as classified by CTCAE 4.0.
The median age was 71.2 years (SD ± 5.3). Comorbidities included cardiovascular disease (20.7%), diabetes (5.2%), chronic obstructive pulmonary disease (2.2%), and hepatitis B (0.7%). Common mutations constituted 71.9% of cases, with uncommon mutations representing 28.1%. Brain metastases were observed in 24.4% of patients. Initial treatment doses were 40 mg for 35.6% of patients and 30 mg for 62.2%. With a median follow-up of 34.3 months, the median TTF was 16.3 months (95% CI: 15.4-19.5), and the median OS was 32.9 months (95% CI: 28.9-37.5). Factors associated with decreased OS included poor performance status, current smoking, and the presence of uncommon mutations. The ORR was 77.8%, with a complete response of 11.1% and a disease control rate of 94.1%. The most common toxicities were dermatologic and mucosal, including diarrhea (55.6%), rash (48.9%), and stomatitis (40.7%), predominantly in grades 1 and 2. Initiating treatment at doses below 40 mg significantly reduced most toxicities compared to the 40 mg dose. The presence of brain metastases did not significantly affect ORR, TTF, or OS. Starting treatment at doses below 40 mg significantly lowered the response rate but did not impact TTF or OS.
First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.
阿法替尼是第二代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，通过随机对照试验和真实世界研究证明对携带 EGFR 突变的非小细胞肺癌（NSCLC）患者有效。老年患者在身体状况和合并症方面具有独特的特征，与年轻患者相比，在选择初始剂量和进行剂量调整方面存在临床实践差异。本研究旨在评估在越南的真实环境中，一线阿法替尼治疗老年 EGFR 突变型 NSCLC 患者的疗效和不良反应。
我们对来自越南 9 家癌症中心的 135 名年龄在 65 岁及以上的患者进行了回顾性分析。这些患者携带药物敏感的 EGFR 突变（不包括新发 T790M），在 2018 年 4 月至 2022 年 6 月期间接受了一线阿法替尼治疗。使用 Kaplan-Meier 法评估无进展生存期（PFS）和总生存期（OS），采用对数秩检验进行比较。次要终点包括根据 RECIST 1.1 评估的总缓解率（ORR）和根据 CTCAE 4.0 分类的不良反应。
中位年龄为 71.2 岁（SD ± 5.3）。合并症包括心血管疾病（20.7%）、糖尿病（5.2%）、慢性阻塞性肺疾病（2.2%）和乙型肝炎（0.7%）。常见突变占 71.9%，罕见突变占 28.1%。24.4%的患者有脑转移。初始治疗剂量为 40 mg 的占 35.6%，30 mg 的占 62.2%。中位随访 34.3 个月，中位 PFS 为 16.3 个月（95%CI：15.4-19.5），中位 OS 为 32.9 个月（95%CI：28.9-37.5）。与 OS 降低相关的因素包括较差的体能状态、当前吸烟和罕见突变的存在。ORR 为 77.8%，完全缓解率为 11.1%，疾病控制率为 94.1%。最常见的毒性是皮肤和黏膜毒性，包括腹泻（55.6%）、皮疹（48.9%）和口腔炎（40.7%），主要为 1 级和 2 级。起始剂量低于 40 mg 与 40 mg 剂量相比，显著降低了大多数毒性。脑转移的存在并未显著影响 ORR、PFS 或 OS。起始剂量低于 40 mg 显著降低了缓解率，但未影响 PFS 或 OS。
在越南多中心真实环境中，一线阿法替尼治疗老年 EGFR 突变型 NSCLC 患者具有显著疗效和可管理的毒性。阿法替尼的疗效得到了证实，具有已知的且可控制的不良反应，支持在该患者人群中使用。
