Liu Frank Xiaoqing, Ou Wanmei, Diede Scott J, Whitman Eric D
Merck & Co., Inc., Kenilworth.
Atlantic Melanoma Center, Atlantic Health System Cancer Care, Morristown, NJ.
Medicine (Baltimore). 2019 Jul;98(30):e16542. doi: 10.1097/MD.0000000000016542.
Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan-Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18-84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03-39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8-29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7-5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.
帕博利珠单抗在美国被批准用于治疗晚期黑色素瘤已超过4年。我们在美国肿瘤临床实践中研究了帕博利珠单抗的实际使用情况及相关结果，包括那些不符合临床试验条件的患者。利用Flatiron Health纵向数据库识别出2014年9月4日至2016年12月31日期间开始使用≥1剂帕博利珠单抗的成年晚期黑色素瘤患者，并随访至2017年12月31日。研究期间参与任何临床试验的患者被排除。采用Kaplan-Meier（KM）方法分析总生存期（OS）和从开始使用帕博利珠单抗起的治疗时间。进行亚组分析以检查包括东部肿瘤协作组（ECOG）体能状态>1、脑转移以及开始使用帕博利珠单抗前使用皮质类固醇等多种患者特征的OS情况。帕博利珠单抗分别作为一线、二线和三线/后续治疗用于315例（59%）、152例（29%）和65例（12%）患者。开始使用帕博利珠单抗时的中位年龄为68岁（范围18 - 84岁）；大多数患者为男性（66%）且为白人（94%）。在有可用数据的患者中，38%患有BRAF突变型黑色素瘤，21%乳酸脱氢酶（LDH）水平升高，23%的ECOG>1。总体而言，18%有脑转移，23%在开始使用帕博利珠单抗前<3个月被开具皮质类固醇药物。中位研究随访时间为12.9个月（范围0.03 - 39.6）。中位OS为21.8个月（95%置信区间[CI] 16.8 - 29.1）；KM 1年和2年生存率分别为61%和48%；帕博利珠单抗治疗的中位时间为4.9个月（95% CI 3.7 - 5.5）。一线使用帕博利珠单抗的中位OS未达到，二线和三线/后续治疗的中位OS分别为13.9个月和12.5个月（对数秩检验P = 0.0095）。ECOG体能状态（PS）为0至1（对比>1）、LDH水平正常（对比升高）以及开始使用帕博利珠单抗前<3个月未开具（对比开具）皮质类固醇药物的患者，其OS明显更好（所有P≤0.0014，对数秩检验）。脑转移（对数秩检验P = 0.22）或BRAF突变状态（对数秩检验P = 0.90）对OS无差异记录。这些发现支持了帕博利珠单抗在真实世界临床环境中的有效性，并为患有晚期黑色素瘤的异质性患者群体（包括那些不符合临床试验条件的患者）接受帕博利珠单抗治疗的患者特征和结果提供了重要见解。
