Abstract：
BACKGROUND: The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials.
METHODS: Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment.
RESULTS: Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively.
CONCLUSIONS: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.
METHODS: Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment.
RESULTS: Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively.
CONCLUSIONS: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.
摘要：
背景：在4项3期临床试验的汇总分析中评估了辅助派姆单抗的安全性。
方法：患者已完全切除IIIA期，IIIB,或美国癌症联合委员会的IIIC黑色素瘤，第7版,标准(AJCC-7;KEYNOTE-054);符合AJCC-8(KEYNOTE-716)的IIB期或IIC黑色素瘤;IB期,II,根据AJCC-7（PEARLS/KEYNOTE-091）或IIIA非小细胞肺癌；或肾切除术/转移切除术后透明细胞肾细胞癌复发风险增加（KEYNOTE-564）。患者每3周接受一次200mg的pembrolizumab（儿科患者为2mg/kg至200mg）或安慰剂，持续约1年。总结了接受≥1剂量治疗的患者的不良事件（AE）。
结果：数据来自4125名接受派姆单抗（n=2060）或安慰剂（n=2065）治疗的患者。pembrolizumab治疗的中位（范围）持续时间为11.1个月（0.0-18.9），安慰剂治疗为11.2个月（0.0-18.1）。治疗相关的AE发生在pembrolizumab组的78.6%(1620/2060)患者(3-5级,16.3%[336/2060])和安慰剂组的58.7%(1212/2065)患者(3-5级,3.5%[72/2065])中。免疫介导的AE(例如肾上腺功能不全，垂体炎,和甲状腺炎）发生在36.2%(746/2060)的pembrolizumab组(3-5级,8.6%[177/2060])和8.4%(174/2065)的安慰剂组(3-5级,1.1%[23/2065]).在免疫介导的AE或输注反应≥1的患者中，在pembrolizumab和安慰剂组中，有35.2％（268/761）和20.2％（39/193）的患者需要全身性皮质类固醇，分别。
结论：辅助派姆单抗显示了可控制的安全性，与晚期疾病的先前报告相当。
方法：患者已完全切除IIIA期，IIIB,或美国癌症联合委员会的IIIC黑色素瘤，第7版,标准(AJCC-7;KEYNOTE-054);符合AJCC-8(KEYNOTE-716)的IIB期或IIC黑色素瘤;IB期,II,根据AJCC-7（PEARLS/KEYNOTE-091）或IIIA非小细胞肺癌；或肾切除术/转移切除术后透明细胞肾细胞癌复发风险增加（KEYNOTE-564）。患者每3周接受一次200mg的pembrolizumab（儿科患者为2mg/kg至200mg）或安慰剂，持续约1年。总结了接受≥1剂量治疗的患者的不良事件（AE）。
结果：数据来自4125名接受派姆单抗（n=2060）或安慰剂（n=2065）治疗的患者。pembrolizumab治疗的中位（范围）持续时间为11.1个月（0.0-18.9），安慰剂治疗为11.2个月（0.0-18.1）。治疗相关的AE发生在pembrolizumab组的78.6%(1620/2060)患者(3-5级,16.3%[336/2060])和安慰剂组的58.7%(1212/2065)患者(3-5级,3.5%[72/2065])中。免疫介导的AE(例如肾上腺功能不全，垂体炎,和甲状腺炎）发生在36.2%(746/2060)的pembrolizumab组(3-5级,8.6%[177/2060])和8.4%(174/2065)的安慰剂组(3-5级,1.1%[23/2065]).在免疫介导的AE或输注反应≥1的患者中，在pembrolizumab和安慰剂组中，有35.2％（268/761）和20.2％（39/193）的患者需要全身性皮质类固醇，分别。
结论：辅助派姆单抗显示了可控制的安全性，与晚期疾病的先前报告相当。
