Brückl Wolfgang M, Reck Martin, Griesinger Frank, Schäfer Harald, Kortsik Cornelius, Gaska Tobias, Rawluk Justyna, Krüger Stefan, Kokowski Konrad, Budweiser Stephan, Ficker Joachim H, Hoffmann Christopher, Schüler Andrea, Laack Eckart
Department of Respiratory Medicine, Allergology and Sleep Medicine, Paracelsus Medical University, General Hospital Nuremberg, Ernst-Nathan-Str.1, Nuremberg, 90419, Germany.
LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
Ther Adv Med Oncol. 2021 May 6;13:17588359211012361. doi: 10.1177/17588359211012361. eCollection 2021.
Lung cancer is a leading cause of cancer-related death in Germany and worldwide. Non-small cell lung cancer (NSCLC) comprises ~80% of lung cancer diagnoses; in White patients, around 10% of NSCLC cases are epidermal growth factor receptor mutation-positive (m+). Head-to-head clinical trials have demonstrated superior efficacy with second-/third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first-generation EGFR TKIs in m+ NSCLC. Data from routine clinical practice are necessary to confirm that clinical trial findings are transferable to real-world populations.
In NCT02047903, a prospective non-interventional study in Germany, patients with m+ NSCLC received first-line afatinib until disease progression or intolerable adverse events. Key objectives were progression-free survival (PFS) rate at 12 months, objective response rate (ORR) and overall survival (OS). Safety/tolerability was also assessed.
Of 152 patients, 106 (69.7%) were female, 20 (13.1%) patients had an uncommon mutation and 51 patients (33.6%) had brain metastases. A starting dose of <40 mg was received by 39 (25.7%) patients. Overall, the 12-month PFS rate was 50.2% while the median PFS was 12.2 months. The ORR was 74.6% and the median OS was 30.4 months. In patients with brain metastases and uncommon mutations, the median PFS was 10.5 and 10.7 months, and the ORR was 77.3% and 83.3%, respectively. Treatment effectiveness was similar in patients with a starting dose of <40 mg (median PFS: 16.4 months; ORR, 81.3%) and a starting dose of 40 mg (median PFS: 10.8 months; ORR, 72.1%). Adverse drug reactions were manageable and consistent with the known afatinib safety profile.
The results support clinical trial data for afatinib in routine clinical practice, including in patients generally excluded from clinical trials. Outcomes were positive in patients with uncommon mutations and in those with brain metastases. Treatment benefit was also seen in patients receiving a <40 mg afatinib starting dose, supporting patient-tailored dosing.
肺癌是德国及全球癌症相关死亡的主要原因。非小细胞肺癌（NSCLC）约占肺癌诊断病例的80%；在白人患者中，约10%的NSCLC病例为表皮生长因子受体突变阳性（m+）。头对头临床试验已证明，第二代/第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）在m+NSCLC中的疗效优于第一代EGFR TKIs。需要来自常规临床实践的数据来证实临床试验结果可应用于真实世界人群。
在德国进行的一项前瞻性非干预性研究NCT02047903中，m+NSCLC患者接受一线阿法替尼治疗，直至疾病进展或出现无法耐受的不良事件。主要目标是12个月时的无进展生存率（PFS）、客观缓解率（ORR）和总生存期（OS）。同时评估安全性/耐受性。
152例患者中，106例（69.7%）为女性，20例（13.1%）患者有罕见突变，51例（33.6%）患者有脑转移。39例（25.7%）患者起始剂量<40mg。总体而言，12个月PFS率为50.2%，中位PFS为12.2个月。ORR为74.6%，中位OS为30.4个月。在有脑转移和罕见突变的患者中，中位PFS分别为10.5个月和10.7个月，ORR分别为77.3%和83.3%。起始剂量<40mg的患者（中位PFS：16.4个月；ORR，81.3%）和起始剂量40mg的患者（中位PFS：10.8个月；ORR，72.1%）的治疗效果相似。药物不良反应可控，与已知的阿法替尼安全性特征一致。
结果支持阿法替尼在常规临床实践中的临床试验数据，包括通常被排除在临床试验之外的患者。在有罕见突变的患者和有脑转移的患者中，结果呈阳性。接受阿法替尼起始剂量<40mg的患者也观察到治疗益处，支持个体化给药。
