Introduction: Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.
Methods: Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.
Results: The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.
Conclusion: Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting.
Implications for practice: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.
摘要
简介。奥希替尼是第三代酪氨酸激酶抑制剂，最初被批准用于治疗具有 T790M 获得性耐药性的表皮生长因子受体 (EGFR) 突变非小细胞肺癌 (NSCLC)，现已被批准用于一线用药。虽然奥希替尼被公认具有中枢神经系统 (CNS) 活性，但支持在未经治疗的脑转移中使用奥希替尼的数据非常有限。我们的研究对比了为出现进展性脑转移患者提供颅脑照射和奥希替尼治疗与奥希替尼单药治疗的临床结果。
方法。通过搜索电子病历数据库，我们确定了 40 名在 2015 年 11 月至 2016 年 12 月期间在斯坦福癌症中心接受奥希替尼治疗的患者。11 名患者出现进展性脑转移且没有接受放射治疗(A 组)，9 名患者出现进展性脑转移且在开始服用奥希替尼的同时接受放射治疗(B 组)，20 名患者在开始服用奥希替尼时处于稳定性脑转移状态(C 组)。我们针对 3 组的患者和疾病特征、影照学反应以及生存结果进行回顾性评估。
结果。CNS 反应率为 32.3%。中位至治疗失败时间 (TTF)、总无进展生存期 (PFS) 和总生存期 (OS) 分别为 10.0 个月 [95% 置信区间 (CI)，4.5–11.8]、8.8 个月(95%CI，6.2–12.1)和 16.2 个月。A 组、B 组和 C 组的中位 TTF 分别为 15.1 个月(95% CI，1.7–28.5)、7.7 个月(95% CI，0–15.5)和 10.7 个月(95% CI，9.0–12.5)。A 组 和 C 组的中位 PFS 分别为 8.8 个月(95% CI，4.3–13.4)和 8.4 个月(95% CI，5.6–11.1)，而 B 组未达到中位 PFS。A 组和 C 组未达到中位 OS，B 组的中位 OS 为 16.2 个月。3 组之间的 TTF、PFS 或 OS 没有明显差异。
结论。在我们的系列研究中，让出现进展性脑转移的患者在开始服用奥希替尼之前接受放射治疗不会延长 TTF、PFS 或 OS。为了最大限度地降低放射治疗相关毒性风险，可以考虑为部分在二线用药中对奥希替尼最初出现反应的伴有脑转移的 EGFR 突变 NSCLC 患者延迟放射治疗。
对临床实践的提示:奥希替尼是第三代表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂，最近被批准用于 EGFR 突变非小细胞肺癌的一线治疗。尽管奥希替尼似乎具有中枢神经系统 (CNS) 活性，但是，大部分临床试验已将出现未经治疗的进展性脑转移的患者排除在外。本研究包含具有稳定性和进展性脑转移的患者以接受奥希替尼治疗，研究结果表明，接受奥希替尼单药治疗的患者与接受奥希替尼和放射手术治疗的患者之间的中位至治疗失败时间、至进展时间和总生存期没有明显差异。这可以支持临床医生为经选的出现未经治疗的脑转移且申请奥希替尼治疗的患者延迟放射治疗的决定
Keywords: Brain metastases; EGFR‐mutant lung cancer; Osimertinib; Stereotactic radiosurgery.
© AlphaMed Press 2018.