School of Medicine, Case Western Reserve University, Cleveland Clinic, Cleveland, Ohio.
Department of Radiation Oncology, Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, California.
Neuro Oncol. 2019 May 6;21(5):659-668. doi: 10.1093/neuonc/noz006.
Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates.
Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis.
Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91).
The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases.
人表皮生长因子受体 2（HER2）阳性的乳腺癌患者在治疗后仍存在颅内复发的高风险，并且在立体定向放射外科（SRS）后颅内失败的发生率增加。我们假设在 SRS 中加入同时使用拉帕替尼会提高颅内完全缓解率。
纳入了 2005 年至 2014 年间接受 SRS 治疗的新诊断为 HER2 扩增型乳腺癌脑转移患者，并根据拉帕替尼治疗时间分为 2 组。观察指标包括根据 RECIST 1.1 标准达到颅内完全缓解或疾病进展的患者比例，以及个体病灶缓解率、远处颅内失败和放射性坏死。
在研究期间，84 例患者的 487 个脑转移灶符合纳入标准。在 138 次治疗过程中，132 个病灶（27%）接受了 SRS 联合拉帕替尼治疗，355 个病灶（73%）接受了单纯 SRS 治疗。与单独接受 SRS 治疗的患者相比，同时接受拉帕替尼治疗的患者完全缓解率更高（35% vs 11%，P=0.008）。基于每个病灶，联合拉帕替尼组的最佳客观缓解率更高（中位数 100% vs 70%的减少，P<0.001）。联合拉帕替尼与 2+级放射性坏死风险增加无关（联合拉帕替尼组 1.0%，无拉帕替尼组 3.5%，P=0.27）。拉帕替尼对远处颅内失败率没有保护作用（48% vs 49%，P=0.91）。
在 SRS 中加入同时使用拉帕替尼可提高 HER2 阳性脑转移患者的完全缓解率。
