PD-1免疫疗法KEYTRUDA(pembrolizumab)为静脉注射用-获美国FDA扩展批准治疗鳞状和非-鳞状非-小细胞肺癌
美国初次批准：2014   公司：Merck & Co.，Inc
最近重大修改-红色为重大修改部分
适应证和用途 10/2015
剂量和给药方法 10/2015
剂量和给药方法(2.4) 01/2015
警告和注意事项 10/2015
警告和注意事项 06/2015
适应证和用途
KEYTRUDA是一个人程序性死亡受体-1(PD-1)-阻断抗体适用为治疗：
⑴不可切除的或转移黑色素瘤和普利姆玛后疾病进展和，如BRAF V600突变阳性，一个BRAF抑制剂患者。
⑵患者其肿瘤表达PD-L1被FDA批准的测试确定有转移NSCLC和有或用含铂化疗后疾病进展。接受KEYTRUDA前用FDA-批准的治疗对这些畸变患者有EGFR或ALK基因组肿瘤畸变。
根据肿瘤反应率和反应的持久性在加速批准下批准这个适应证。尚未确定在生存或疾病相关症状中改善。对这个适应证的继续批准可能取决于在验证性试验中临床获益的验证和描述。
剂量和给药方法
⑴ 每3周给予2 mg/kg作为历时30分钟静脉输注。
⑵  静脉输注前重建和稀释。
剂型和规格
⑴ 为注射：50mg，为重建在一次性使用小瓶中冰冻干燥粉。
⑵  注射用: 100mg/4mL(25 mg/mL)溶液在一次性使用小瓶。
禁忌证
无。
警告和注意事项
⑴免疫-介导肺炎:对中度不给，和永远终止对严重，危及生命或复发中度肺炎。
⑵免疫-介导结肠炎:对中度或严重不给，和对危及生命结肠炎永远终止。
⑶免疫-介导肝炎: 监视肝功能中变化。根据肝酶升高严重程度，不给或终止。
⑷ 免疫-介导内分泌病:
 ① 垂体炎:对中度不给和对严重或危及生命垂体炎不给或永久终止。
 ②甲状腺疾病: 监视甲状腺功能。对严重或危及生命甲状腺功能亢进不给或永远终止。
 ③1型糖尿病: 监视高血糖。在严重高血糖病例不给 KEYTRUDA。
⑸ 免疫-介导肾炎: 监视肾功能变化。对中度不给，和对严重或危及生命肾炎永远终止。
⑹ 输注-相关反应: 停止输注和对严重或危及生命 输注反应永远终止KEYTRUDA。
⑺ 胚胎胎儿毒性: KEYTRUDA可致胎儿危害。忠告生殖潜能女性对胎儿潜在风险。
不良反应
最常见不良反应(报告在≥20%患者)有：
⑴黑色素瘤包括疲劳，咳嗽，恶心，瘙痒，皮疹，食欲减低, 便秘，关节痛，和腹泻。
⑵NSCLC 包括疲乏，食欲减退，呼吸困难和咳嗽。
特殊人群中使用
哺乳母亲：终止哺乳或终止KEYTRUDA。

KEYTRUDA(PEMBROLIZUMAB)POWDER, FOR INJECTION SOLUTION, LYOPHILIZED POWDER
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. KEYTRUDA is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
PD-L1 = programmed death ligand 1; EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase.
SELECTED SAFETY INFORMATION FOR MELANOMA
Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA® (pembrolizumab) for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.
Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia.
Nephritis occurred in 3 (0.7%) patients, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur. The following clinically significant immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, severe dermatitis including bullous pemphigoid, myasthenic syndrome, optic neuritis, and rhabdomyolysis.
For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.
KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients. Adverse reactions, reported in at least two patients, that led to discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain. Serious adverse reactions occurred in 36% of patients. The most frequent serious adverse reactions, reported in 2% or more of patients, were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).
No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA.
Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.
SELECTED SAFETY INFORMATION FOR NSCLC
Pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
Hepatitis occurred in patients receiving KEYTRUDA® (pembrolizumab). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 1 (0.2 %) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or Grade 4 hypophysitis.
Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%). Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.
Nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following steroid taper. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant, immune-mediated adverse reactions occurred in patients treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum sickness, myasthenia gravis, bullous pemphigoid, and Guillain-Barré syndrome.
Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis.
The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), decreased appetite (25%), dyspnea (23%), and cough (29%).
No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

PD-1免疫疗法Keytruda治疗恶性胸膜间皮瘤
近日，默沙东抗癌新药PD-1免疫疗法Keytruda（pembrolizumab）治疗实体瘤的一项Ib期KEYNOTE-028研究的首批数据。该研究是一项多组、非随机研究，在当前疗法不适合或无响应的320例PD-L1阳性晚期实体瘤患者中开展，旨在调查Keytruda（10mg/kg，每2周给药一次）单药疗法治疗20种难治性肿瘤的安全性、耐受性和抗肿瘤活性。
此次公布的是Keytruda治疗25例胸膜间皮瘤（pleural mesothelioma，PM）患者的疗效和安全性数据。数据显示，Keytruda治疗取得了28%的总缓解率（ORR），此外有48%的患者病情稳定，疾病控制率达到了76%。在分析数据时，有40%（n=10/25）的患者仍然在接受治疗。该研究中，不良事件与以往报道的Keytruda安全性数据一致。治疗相关的最常见不良事件（发生于≥20%患者）包括疲劳（24%）、恶心（24%）。研究中未发生治疗相关不良事件的停药，也没有发生治疗相关的死亡事件。
相关数据已提交至4月18-22日举行的2015年美国癌症研究协会（AACR）年会上。据悉，这也是KEYNOTE-028研究的首批数据。
默沙东表示，该部分研究中所观察到的高达76%的疾病控制率数据非常鼓舞人心，支持了进一步调查Keytruda治疗恶性胸膜间皮瘤的临床潜力。
胸膜间皮瘤（PM）是一种原发于胸膜间皮的罕见、侵袭性、恶性肿瘤，治疗选择极其有限。外科手术是该病的主要治疗方法，术后辅助放疗能控制肿瘤的局部复发，并延长生存期。
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产地国家：美国
原产地英文商品名:
KEYTRUDA 100mg/4ml（25mg/ml）/vial 1vial
原产地英文药品名:
pembrolizumab
中文参考商品译名:
KEYTRUDA注射液  100毫克/4毫升(25毫克/毫升)/瓶 1瓶
中文参考药品译名:
派姆单抗
生产厂家中文参考译名:
默克
生产厂家英文名:
Merck 
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产地国家：美国
原产地英文商品名:
KEYTRUDA 50MG SINGLE USE VIAL
原产地英文药品名:
pembrolizumab
中文参考商品译名:
KEYTRUDA注射液  50毫克/毫升瓶
中文参考药品译名:
派姆单抗
生产厂家中文参考译名:
默克
生产厂家英文名:
Merck 
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产地国家：香港
原产地英文商品名:
KEYTRUDA Injection 100mg/4ml（25mg/ml）/Vial
原产地英文药品名:
pembrolizumab
中文参考商品译名:
KEYTRUDA注射液  100毫克/4毫升(25毫克/毫升)/瓶
中文参考药品译名:
派姆单抗
生产厂家中文参考译名:
默克
生产厂家英文名:
Merck 
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产地国家：德国
原产地英文商品名:
KEYTRUDA 100mg/4ml（25mg/ml）/vial 1vial
原产地英文药品名:
pembrolizumab
中文参考商品译名:
KEYTRUDA注射液  100毫克/4毫升(25毫克/毫升)/瓶 1瓶
中文参考药品译名:
派姆单抗
生产厂家中文参考译名:
默克
生产厂家英文名:
Merck 
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产地国家：德国
原产地英文商品名:
KEYTRUDA 50MG SINGLE USE VIAL
原产地英文药品名:
pembrolizumab
中文参考商品译名:
KEYTRUDA注射液  50毫克/毫升/瓶
中文参考药品译名:
派姆单抗
生产厂家中文参考译名:
默克
生产厂家英文名:
Merck