Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Br J Cancer. 2020 Nov;123(10):1535-1542. doi: 10.1038/s41416-020-01044-8. Epub 2020 Sep 1.
Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). It is important to understand both safety and efficacy in a real-world and trial-ineligible cSCC population. We aimed to evaluate safety, efficacy and molecular insights among a broader cSCC population, including immunosuppressed patients, treated with immune checkpoint inhibitors (CPI).
We present a cohort of advanced cSCC patients (n = 61) treated from 2015 to 2020 evaluating the best overall response (BOR) (RECISTv1.1) to CPI therapy, immune-related adverse events (irAEs) and tumour mutational burden (TMB) to correlate with outcomes. A validated geriatric scoring index (CIRS-G) was utilised to assess comorbidities among patients ≥75. These data were compared with published clinical trial results among the broader cSCC population.
BOR to CPI was lower among the entire cohort when compared with trial data (31.5 vs. 48%, P < 0.01), with higher rates of progression (59 vs. 16.5%, P < 0.01), regardless of immunosuppression history or age. Grade 3+ irAEs were more common among responders (P = 0.02), while pre-treatment lymphocyte count and TMB predicted response (P = 0.02).
We demonstrate comparatively lower response rates to CPI among real-world cSCC patients not explained by older age or immunosuppression history alone. Immune-related toxicity, absolute lymphocyte count and TMB predicted CPI response.
免疫疗法彻底改变了晚期皮肤鳞状细胞癌（cSCC）的治疗方法。了解免疫检查点抑制剂（CPI）在真实世界和不适合临床试验的 cSCC 人群中的安全性和疗效非常重要。我们旨在评估更广泛的 cSCC 人群（包括免疫抑制患者）接受 CPI 治疗后的安全性、疗效和分子见解。
我们报告了一组从 2015 年至 2020 年接受治疗的晚期 cSCC 患者（n=61）队列，评估了 CPI 治疗的最佳总体缓解（BOR）（RECISTv1.1）、免疫相关不良事件（irAE）和肿瘤突变负担（TMB）与结局的相关性。使用经过验证的老年评分指数（CIRS-G）评估≥75 岁患者的合并症。这些数据与更广泛的 cSCC 人群的临床试验结果进行了比较。
与临床试验数据相比，整个队列对 CPI 的 BOR 较低（31.5%比 48%，P<0.01），进展率更高（59%比 16.5%，P<0.01），无论是否有免疫抑制史或年龄。在反应者中更常见 3+级 irAE（P=0.02），而治疗前淋巴细胞计数和 TMB 预测了反应（P=0.02）。
我们证明了在真实世界的 cSCC 患者中，CPI 的反应率相对较低，这不能仅用年龄较大或免疫抑制史来解释。免疫相关毒性、绝对淋巴细胞计数和 TMB 预测了 CPI 的反应。
