Department of Oncology, Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London, United Kingdom.
PLoS One. 2013 May 7;8(5):e62543. doi: 10.1371/journal.pone.0062543. Print 2013.
Analysis of circulating tumor cells (CTCs) provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.
Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.
There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43%) individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.
This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.
Clinical trials.gov NCT00820924.
循环肿瘤细胞（CTC）的分析为具有CTC 导向治疗潜力的癌症亚群提供了实时测量。我们研究了 lapatinib（同时结合 HER2 和 EGFR）是否能诱导 EGFR 阳性 CTC 池的耗竭，这可能会带来临床获益。
招募了转移性乳腺癌和 HER2 非扩增原发肿瘤且有 EGFR 阳性 CTC 的患者，并进行了标准的两步 2 期临床试验，每天给予 lapatinib 1500mg。
在第一次分析时，由于筛选出的 43 名患者中有 16 名患者入组，因此没有出现任何导致试验终止的反应。在 14 名符合疗效分析的患者中，有 6 名（43%）观察到 CTC 减少，其中大多数患者的 EGFR 阳性 CTC 池减少幅度更大。
这是第一项关于 CTC 导向治疗的研究之一，表明 lapatinib 单药治疗通过减少 HER2 非扩增原发肿瘤中 EGFR 阳性 CTC 池，没有任何明显的临床效果。我们试图扩大有资格接受靶向治疗的患者群体的尝试没有成功；在未来几年，克隆群体在癌症生物学和控制它们的治疗策略中的作用将需要广泛评估。
Clinicaltrials.gov NCT00820924。
