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年龄对黑色素瘤患者免疫治疗结局的影响

Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.

作者信息

Betof Allison S, Nipp Ryan D, Giobbie-Hurder Anita, Johnpulle Romany A N, Rubin Krista, Rubinstein Samuel M, Flaherty Keith T, Lawrence Donald P, Johnson Douglas B, Sullivan Ryan J

机构信息

Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.

Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

出版信息

Oncologist. 2017 Aug;22(8):963-971. doi: 10.1634/theoncologist.2016-0450. Epub 2017 May 5.

Abstract

BACKGROUND

Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers.

METHODS

We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015. We used Kaplan-Meier and Cox regression analyses to assess OS and PFS and identify factors associated with these outcomes. We also compared rates of autoimmune toxicity across age groups.

RESULTS

Of 254 patients, 57 (22.4%) were <50 years old, 85 (33.5%) were age 50-64, 65 (25.6%) were age 65-74, and 47 (18.5%) were ≥75 years. Across age groups, no differences existed in median OS (age <50: 22.9 months, age 50-64: 25.3 months, age 65-74: 22.0 months, age ≥75: 24.3 months) or PFS (age <50: 4.1 months, age 50-64: 6.5 months, age 65-74: 5.4 months, age ≥75: 7.9 months). The presence of liver metastases and elevated pre-treatment lactate dehydrogenase (LDH) were associated with reduced OS. Presence of liver metastasis, pretreatment LDH, BRAF mutation, and type of melanoma correlated with PFS. Overall, 110 patients (43.3%) experienced immune-mediated toxicities; 25 (9.8%) had colitis and 26 (10.2%) had endocrine toxicity. Rates of colitis, hepatitis, and pneumonitis did not differ across age groups.

CONCLUSION

We demonstrated that patients could safely tolerate anti-PD1/PDL-1 mAb therapy and achieve similar outcomes regardless of their age.

IMPLICATIONS FOR PRACTICE

Immunotherapy has revolutionized treatment for patients with metastatic melanoma, yet data are lacking regarding the effectiveness and tolerability of these treatments for older patients. In this study, we demonstrated that patients with melanoma safely tolerate immunotherapy and achieve similar outcomes regardless of their age. Specifically, we utilized data from two academic cancer centers and found no significant difference in overall survival, progression free survival, or immune-related toxicities, other than arthritis, across age groups. As the population ages, studies such as this will become critical to help us understand how best to treat older adults with cancer.

摘要

背景

靶向PD-1/PD-L1的单克隆抗体(mAb)彻底改变了黑色素瘤的治疗方式,但关于各年龄组有效性和耐受性的数据有限。我们试图确定年龄对在两个学术医学中心接受抗PD-1/抗PD-L1 mAb治疗的患者的总生存期(OS)、无进展生存期(PFS)以及免疫介导毒性发生率的影响。

方法

我们回顾性收集了2009年5月至2015年4月期间所有接受抗PD-1/PD-L1 mAb治疗的转移性黑色素瘤患者的数据。我们使用Kaplan-Meier和Cox回归分析来评估OS和PFS,并确定与这些结果相关的因素。我们还比较了各年龄组自身免疫毒性的发生率。

结果

在254例患者中,57例(22.4%)年龄小于50岁,85例(33.5%)年龄在50 - 64岁之间,65例(25.6%)年龄在65 - 74岁之间,47例(18.5%)年龄大于等于75岁。在各年龄组中,中位OS(年龄小于50岁:22.9个月,年龄50 - 64岁:25.3个月,年龄65 - 74岁:22.0个月,年龄大于等于75岁:24.3个月)或PFS(年龄小于50岁:4.1个月,年龄50 - 64岁:6.5个月,年龄65 - 74岁:5.4个月,年龄大于等于75岁:7.9个月)没有差异。肝转移的存在和治疗前乳酸脱氢酶(LDH)升高与OS降低相关。肝转移的存在、治疗前LDH、BRAF突变和黑色素瘤类型与PFS相关。总体而言,110例患者(43.3%)经历了免疫介导的毒性;25例(共9.8%)患有结肠炎,26例(共10.2%)患有内分泌毒性。各年龄组的结肠炎、肝炎和肺炎发生率没有差异。

结论

我们证明患者能够安全耐受抗PD1/PDL-1 mAb治疗,无论年龄大小均可获得相似的结果。

对实践的启示

免疫疗法彻底改变了转移性黑色素瘤患者的治疗方式,但缺乏这些治疗方法对老年患者有效性和耐受性的数据。在本研究中,我们证明黑色素瘤患者能够安全耐受免疫疗法,无论年龄大小均可获得相似的结果。具体而言,我们利用了两个学术癌症中心的数据,发现各年龄组在总生存期、无进展生存期或除关节炎外的免疫相关毒性方面没有显著差异。随着人口老龄化,此类研究对于帮助我们了解如何最好地治疗老年癌症患者将变得至关重要。

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