Medical Oncology, Dana-Farber Cancer Institute, USA.
Hematology/Oncology, Miami Cancer Institute, USA.
Eur J Cancer. 2019 May;113:1-9. doi: 10.1016/j.ejca.2019.03.004. Epub 2019 Apr 4.
The activity that the immune checkpoint inhibitor (ICI) cemiplimab has recently demonstrated has led to a paradigm shift in the management of patients with advanced cutaneous squamous cell carcinoma (cSCC). To identify predictive biomarkers of response to ICIs in advanced cSCC, we studied 33 patients who received ICI therapy at the Dana-Farber/Harvard Cancer Center (DF/HCC) and analysed sequencing data for a subset of these patients.
We collected clinical data using electronic health records and genomic data using the institutional OncoPanel platform of the DF/HCC. We compared tumour genomics with data from previously sequenced cSCC cohorts.
We observed high tumour mutational burden regardless of smoking status and response to ICI and longer median overall survival among those patients who achieved an ICI response. We compared the genetic data from our cohort with data from other cohorts that included fewer patients with distant metastatic disease. Although our cohort had a similar genetic landscape to those of comparator cohorts, mutations in PIK3C2B were more common in our study. In our cohort, copy number alterations (CNAs) in the 3q chromosomal arm appeared to predict response to ICI therapy.
CNAs in the 21-27 bands of chromosome arm 3q, a region that includes PIK3CA, ETV5 and BCL6, may represent predictors of response to ICI and may be candidates for drug targeting in combination or sequence with ICI agents.
免疫检查点抑制剂（ICI）西米普利单抗最近表现出的活性，导致了晚期皮肤鳞状细胞癌（cSCC）患者管理的范式转变。为了确定晚期 cSCC 对 ICI 反应的预测生物标志物，我们研究了在达纳-法伯/哈佛癌症中心（DF/HCC）接受 ICI 治疗的 33 名患者，并对其中一部分患者的测序数据进行了分析。
我们使用电子病历收集临床数据，并使用 DF/HCC 的机构 OncoPanel 平台收集基因组数据。我们将肿瘤基因组学与以前测序的 cSCC 队列的数据进行了比较。
无论吸烟状态和对 ICI 的反应如何，我们都观察到高肿瘤突变负担，并且对 ICI 有反应的患者的中位总生存期更长。我们将我们的队列的遗传数据与包括较少远处转移性疾病患者的其他队列的数据进行了比较。尽管我们的队列与比较队列具有相似的遗传特征，但 PIK3C2B 中的突变在我们的研究中更为常见。在我们的队列中，3q 染色体臂的拷贝数改变（CNAs）似乎预示着对 ICI 治疗的反应。
染色体臂 3q 的 21-27 带中的 CNA，该区域包括 PIK3CA、ETV5 和 BCL6，可能是对 ICI 反应的预测因子，并且可能是与 ICI 药物联合或序列联合进行药物靶向的候选药物。
