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Pembrolizumab（Keytruda®）获FDA批准作为非小细胞肺癌的一线治疗
美国食品和药物管理局（FDA）已经批准了免疫检查点抑制剂Pembrolizumab（Keytruda®）与化疗联合用作转移性非小细胞肺癌（NSCLC）患者的一线治疗。
5月10日，该药物被批准与培美曲塞（Alimta®）和卡铂一起用于以前未经治疗的晚期非鳞状NSCLC患者--无论其肿瘤是否表达PD-L1。
肿瘤细胞上的PD-L1通过与T细胞上的另一种蛋白质PD-1结合来抑制免疫活性; pembrolizumab通过结合PD-1阻止这种相互作用。
Pembrolizumab先前被批准用于NSCLC中的另外两种适应症：一是用作至少有50％肿瘤细胞表达PD-L1的转移性NSCLC的一线治疗，二是作为在铂基化疗后肿瘤发生进展并且至少有1%的肿瘤细胞表达PD-L1的转移性NSCLC的患者的二线治疗。
对于这两种适应症，PD-L1表达水平必须通过FDA批准的测试来确定。最新批准不需要测量PD-L1表达水平。
这种对pembrolizumab的新批准是这种药物系列中最新的一个。在过去的2个月中，pembrolizumab被批准用于治疗一些膀胱癌和霍奇金淋巴瘤患者，并且首选在那些具有破坏至少两种DNA修复相关突变的肿瘤中使用。它也被批准用于治疗头颈癌和黑色素瘤。
检查点抑制剂越来越多地用于治疗NSCLC。除了对pembrolizumab的这一新批准之外，阿替唑单抗（Tecentriq®）在10月份被批准用于转移性NSCLC，而2015年尼莫单抗（Opdivo®）成为第一个被批准用于治疗肺癌的免疫治疗药物。
免疫治疗加化疗
这种对pembrolizumab的新批准是基于123例晚期或转移性非鳞状NSCLC患者的EGFR基因突变或ALK基因改变的II期临床试验的结果，目前已有靶向治疗。试验中的患者以前没有接受过治疗，随机分配到单独接受pembrolizumab加化疗或pembrolizumab加化疗的实验组中
在试验中，接受pembrolizumab和化疗的患者中有55％对治疗至少有部分反应，而单独接受化疗的患者中有29％。两组中位无进展生存期分别为13个月和8.9个月。
接受pembrolizumab化疗的患者中最常见的严重副作用包括疲劳，呼吸困难（呼吸急促）和恶心。pembrolizumab组中的患者较单独化疗组的患者更容易有副作用。由于严重的副作用----最常见的是急性肾损伤，因此有10％的患者中途停药。
研究人员进一步分析了患者肿瘤中PD-L1的表达情况，根据肿瘤具有PD-L1表达低于1％的细胞和表达高于1％的细胞定义了两个亚组。但是由于每组的样本量较小，因此需要更多的研究来评估PD-L1表达与用pembrolizumab加化疗联合治疗的反应之间的关系。
没有参与试验的斯隆凯特琳纪念中心肿瘤学家Gregory Riely博士说，由于不是基于确定患者肿瘤中的生物标志物，所以对这一最新的药物批准有一些争议。
Riely博士说：“我的恐惧是，使用这种免疫治疗加化学疗法的药物组合基本上可用于所有患有非鳞状细胞癌的非小细胞肺癌患者，这可以使所有患者免于生物标志物的检测。如果发生这种情况，那些不能从免疫治疗药物中受益的患者可能会接受治疗，而不能从化疗中获益的患者也可以获得治疗。”
他说，“例如，有资格获得这种新药物治疗的患者人群中，仅有30％的肿瘤中PD-L1高表达。”具有PD-L1高表达的NSCLC使用pembrolizumab作为一线治疗这一方案得到批准前，临床试验显示这些患者比单独使用pembrolizumab比接受化疗的效果更好。
未来研究
Riely博士指出，因为这项批准目前所依据的临床试验相对较少，所以FDA需要进一步研究以证实pembrolizumab的临床获益。
从III期临床试验用的570例患者的初步结果来看，预计在未来一年内，“我们会很快知道这些是否[二期]实验的结果可靠。” Riely博士说。
他指出，有几个即将进行的实验将用于探索免疫治疗及化疗以及两者联合应用的作用。他说，“未来我们会得到更多的信息来了解这种联合疗法是否有好的意义。”
原文链接https://www.cancer.gov/news-events/cancer-currents-blog/2017/fda-pembrolizumab-lung-expanded
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287
Keytruda (Pembrolizumab for Injection)
KEYTRUDA is a prescription medicine used to treat:
•a kind of skin cancer called melanoma. It may be used when your melanoma has spread or cannot be removed by surgery (advanced melanoma).
•a kind of lung cancer called non–small cell lung cancer (NSCLC). ◦It may be used alone as your first treatment when your lung cancer has spread (advanced NSCLC) and tests positive for “PD-L1” and your tumor does not have an abnormal “EGFR” or “ALK” gene.
◦It may also be used alone for advanced NSCLC if you have tried chemotherapy that contains platinum and it did not work or is no longer working and your lung cancer tests positive for “PD-L1” and, if your tumor has an abnormal “EGFR” or “ALK” gene, you have also received an “EGFR” or “ALK” inhibitor medicine that did not work or is no longer working.
•a kind of cancer called head and neck squamous cell cancer (HNSCC). It may be used when your HNSCC has returned or spread and you have received chemotherapy that contains platinum and it did not work or is no longer working.
•a kind of cancer called classical Hodgkin lymphoma (cHL). KEYTRUDA may be used for cHL in adults and children when you have tried a treatment and it did not work or when your cHL has returned after you received 3 or more types of treatment.
•a kind of bladder or urinary tract cancer when it has spread or cannot be removed by surgery (advanced urothelial cancer) and you are not able to receive chemotherapy that contains a medicine called cisplatin, or you have received chemotherapy that contains platinum, and it did not work or is no longer working.
•a kind of cancer that is shown by a laboratory test to be a microsatellite instability-high (MSI-H) or a mismatch repair deficient (dMMR) solid tumor. KEYTRUDA may be used in adults and children to treat: ◦cancer that has spread or cannot be removed by surgery (advanced cancer), and
◦has progressed following treatment, and you have no satisfactory treatment options, or
◦you have colon or rectal cancer, and you have received chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan but it did not work or is no longer working.
It is not known if KEYTRUDA is safe and effective in children with MSI-H cancers of the brain or spinal cord (central nervous system cancers).
PD-L1 = programmed death ligand 1;
EGFR = epidermal growth factor receptor;
ALK = anaplastic lymphoma kinase.
Important Safety Information About KEYTRUDA® (pembrolizumab)
KEYTRUDA is a medicine that may treat certain cancers by working with your immune system. KEYTRUDA can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.
Call or see your doctor right away if you develop any symptoms of the following problems or these symptoms get worse:
Lung problems (pneumonitis). Symptoms of pneumonitis may include shortness of breath, chest pain, or new or worse cough.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea or more bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; or severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine, feeling less hungry than usual, or bleeding or bruising more easily than normal.
Hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas). Signs and symptoms that your hormone glands are not working properly may include rapid heartbeat, weight loss or weight gain, increased sweating, feeling more hungry or thirsty, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, muscle aches, dizziness or fainting, or headaches that will not go away or unusual headache.
Kidney problems, including nephritis and kidney failure. Signs of kidney problems may include change in the amount or color of your urine.
Skin problems. Signs of skin problems may include rash, itching, blisters, peeling or skin sores, or painful sores or ulcers in your mouth or in your nose, throat, or genital area.
Problems in other organs. Signs of these problems may include changes in eyesight, severe or persistent muscle or joint pains, severe muscle weakness, or low red blood cells (anemia), shortness of breath, irregular heartbeat, feeling tired, or chest pain (myocarditis).
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs and symptoms of infusion reactions may include chills or shaking, shortness of breath or wheezing, itching or rash, flushing, dizziness, fever, or feeling like passing out.
Rejection of a transplanted organ. People who have had an organ transplant may have an increased risk of organ transplant rejection if they are treated with KEYTRUDA.
Complications of stem cell transplantation that uses donor stem cells (allogeneic) after treatment with KEYTRUDA. These complications can be severe and can lead to death. Your doctor will monitor you for signs of complications if you are an allogeneic stem cell transplant recipient.
Getting medical treatment right away may help keep these problems from becoming more serious. Your doctor will check you for these problems during treatment with KEYTRUDA. Your doctor may treat you with corticosteroid or hormone replacement medicines. Your doctor may also need to delay or completely stop treatment with KEYTRUDA if you have severe side effects.
Before you receive KEYTRUDA, tell your doctor if you have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus; have had an organ transplant; have lung or breathing problems; have liver problems; or have any other medical problems.
If you are pregnant or plan to become pregnant, tell your doctor. KEYTRUDA can harm your unborn baby. Females who are able to become pregnant should use an effective method of birth control during treatment and for at least 4 months after the final dose of KEYTRUDA. Tell your doctor right away if you become pregnant during treatment with KEYTRUDA.
If you are breastfeeding or plan to breastfeed, tell your doctor. It is not known if KEYTRUDA passes into your breast milk. Do not breastfeed during treatment with KEYTRUDA and for 4 months after your final dose of KEYTRUDA.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Common side effects of KEYTRUDA include feeling tired, itching, diarrhea, decreased appetite, rash, fever, cough, shortness of breath, pain in muscles, bones or joints, constipation, and nausea.
In children, feeling tired, vomiting and stomach-area (abdominal) pain, and increased levels of liver enzymes and decreased levels of salt (sodium) in the blood are more common than in adults.
These are not all the possible side effects of KEYTRUDA. |
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