非小细胞肺癌是常见的肺癌类型，占肺癌中的80% (American Lung Association, 2020)。非小细胞肺癌晚期的标准治疗手段是含铂双药化疗。含铂双药化疗包括一个三代抗癌药物，及一个含铂类的药物 (如顺铂和卡铂）。顺铂和卡铂通过破坏癌细胞中的DNA结构来杀死体内的癌细胞 (Nature, 2017)。不同于小细胞肺癌，非小细胞肺癌转移到其他器官较为缓慢，因此化疗手段对非小细胞肺癌治疗成效并不明显。(MedicineNet, 2020).
免疫治疗是当前的研究焦点，3-4期肺癌病人的治疗方案中往往会包含化疗与免疫治疗(National Cancer Institute, 2020)。免疫治疗，如免疫检查点抑制剂，会通过调动身体的免疫系统来抵抗癌症的入侵。免疫治疗有两个主要的功能：一是提高身体免疫力，二是训练人体免疫系统抵御癌细胞 (SCNOW, 2019)。目前，美国已有四种适用于肺癌的免疫治疗药物得到FDA批准，分别是Tecentriq® (atezolizumab)、Imfinzi® (durvalumab)、Opdivo® (nivolumab) 和 Keytruda® (pembrolizumab)。以上四种免疫疗法可以通过抑制PD-1和PD-L1这两种蛋白质来提升和训练免疫系统。PD-1是一种在免疫细胞上的蛋白质，而PD-L1是一种在癌细胞上的蛋白质。当免疫细胞攻击癌细胞时，PD-1将与PD-L1结合，使免疫细胞失效。这会让癌细胞躲避免疫细胞的攻击。免疫治疗药物可以阻止这两个蛋白质之间的结合，让癌细胞无处可逃 (National Cancer Institute, 2020)。
Imfinzi®是肺癌治疗的最新进展之一。2017年5月，FDA批准Imfinzi®于用于3期非小细胞肺癌的治疗。Imfinzi®是第一个针对无法接受手术，且放化疗后病情也没有进展的病人的免疫治疗药物。Imfinzi®可以延缓癌症恶化进程，以此来帮助癌症患者 (American Cancer Association, 2020)。
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer (American Lung Association, 2020). The standard course of treatment in metastatic NSCLC, known as platinum-based doublet, consists of a platinum compound plus a third-generation anticancer drug. Platinum compound, including cisplatin and carboplatin, is a class of chemotherapy that kills cancer cells by causing structural damage to DNA inside of cancer cells (Nature, 2017). Unlike small cell lung cancer (SCLC), NSCLC spreads more slowly to other parts of the body than SCLC, but at the same time, it is not as sensitive to chemotherapy (MedicineNet, 2020).
Immunotherapy, often used along with chemotherapy for stage 3 and 4 patients, is a major focus in recent studies (National Cancer Institute, 2020). Immunotherapy, such as immune checkpoint inhibitors, triggers your own immune system to fight against cancer. Immunotherapy has two main functions. It improves the efficiency of the immune system, and it trains the immune system to fight against cancer cells (SCNOW, 2019). Current immunotherapy for lung cancer includes Tecentriq® (atezolizumab), Imfinzi® (durvalumab), Opdivo® (nivolumab), and Keytruda® (pembrolizumab). These medications boost and train your immune system to fight against cancer cells by inhibiting PD-1 or PD-L1 proteins. PD-1 is a protein found on immune cells, while PD-L1 is a protein found on cancer cells. When immune cells attack cancer cells, the binding of PD-1 and PD-L1 will deactivate immune cells. Cancer cells will, in consequence, escape from being killed by the immune system. To prevent the inactivation of immune cells, immunotherapy is designed to block the binding of these two proteins (National Cancer Institute, 2020)。
Imfinzi®, approved by the FDA for stage 3 NSCLC in May 2017, is one of the newest lung cancer advances. Imfinzi is the first immunotherapy targeted towards patients who are not candidates for surgery and have not progressed after chemotherapy and radiation therapy. It can benefit lung cancer patients by slowing the progression of disease over time (American Cancer Association, 2020)。
To learn more about lung cancer treatment plans, schedule a consultation with a world-class U.S. medical oncologist through RangeLight Health today
肺癌是中国排名第一位、美国排名第二位的癌种 (Thorac Cancer, 2019)。非小细胞肺癌则属于肺癌中发病率最高的类型。每年约有80%到85%的肺癌患者被确诊为非小细胞性肺癌(Ann Oncol, 2016)。非小细胞肺癌的治疗方案往往与其分期 (程度）有关，早期患者如0期或1期，病人可能只需要进行外科手术；非小细胞肺癌后期如3期，治疗方案需结合病人的整体健康状况与疾病负担来防止癌症复发或扩散。后期治疗方案可能包含外科手术、放疗、化疗、免疫治疗 (例如英飞凡®/度伐利尤单抗）中的一项或多项。(American Cancer Society, 2019)
科学家与医生们正积极探索更多非小细胞肺癌的治疗方式。截至发稿日，美国已有2539个针对非小细胞肺癌的临床试验，其中540个临床试验开放入组 (Clinicaltrials.gov, 2020) 。赛诺菲的Libtayo®(cemiplimab)已被批准用于肿瘤细胞中PD-L1阳性大于50%的非小细胞肺癌患者。三期试验表明，相较于标准化疗，Libtayo®治疗降低了患者32.4%的死亡率 (Sanofi, 2020) 。武田制药正在研发一种针对表皮生长因子受体 (EGFR) 突变的抗肿瘤新药，Mobocertinib (TAK-788) (Takeda, 2020)。表皮生长因子受体突变是一种会导致细胞癌变的基因变异。试验证明，中国48%的肺癌病人存在表皮生长因子受体突变，该突变在美国患者中的发生率为23% (American Journal of Cancer Research, 2015) 。然而，国家调查数据显示，仅有9.6%的中国患者针对此基因突变进行过检测，这意味着大部分病人可能失去了获得更多靶向治疗的机会 (Journal of Thoracic Oncology, 2016) 。表皮生长因子受体突变的4期病人选择靶向治疗将比化疗有着更轻的副作用与更高的总体生存率。
Lung cancer is the most common cancer in China and the second most common cancer in the United States (Thorac Cancer, 2019). Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer. Approximately 80 to 85% of patients are diagnosed with non-small cell lung cancer among all lung cancer diagnoses each year (Ann Oncol, 2016). The treatment plans of non-small cell lung cancer are usually based on the stage of cancer. For early stages from stage 0 and stage 1, a patient may need only surgery. For later stages, such as stage 3, a combination of surgery, radiation, chemotherapy, and immunotherapy (for example, Imfinzi) may be indicated based on the patient’s health status and disease burden to prevent the cancer from recurring or spreading (American Cancer Society, 2019)
Lung cancer, like all the other types of cancer, is the result of gene mutations. Therefore, newer drug developments for cancer are mainly targeted therapies and immune therapies, as they can target the mutant gene or cancer cell and have a more tolerable side effect profile.
Scientists and physicians are actively working to advance lung cancer treatments. There are a total of 2539 studies focusing on NSCLC, with 540 studies open in the United States (Clinicaltrials.gov, 2020) . Libtayo® (cemiplimab) by Sanofi targets NSCLC patients who tested positive for a protein called PD-L1 in more than 50% of tumor cells. The phase 3 results have shown a significant decrease in the risk of death by 32.4% with Libtayo® alone compared to standard chemotherapy (Sanofi, 2020) . Takeda Pharmaceutical is investigating a new anti-cancer drug, Mobocertinib (TAK-788), which focuses on NSCLC patients with a specific epidermal growth factor receptor (EGFR) mutation (Takeda, 2020) . EGFR mutation is a genetic mutation that results in abnormal cell growth. Studies showed that 48% of patients with lung cancer in China have EGFR gene mutation, compared to 23% of patients with EGFR mutation in America (American Journal of Cancer Research, 2015) . However, national survey data showed that only 9.6% of NSCLC patients in China were tested for EGFR mutation (Journal of Thoracic Oncology, 2016) , meaning that many patients may miss out on the opportunity to try more targeted therapies. Targeted therapies for stage IV disease with EGFR mutations are better tolerated by patients than standard chemotherapies and are associated with significantly improved overall survival rates.
Want to learn more about NSCLC clinical trials in the U.S.? Contact RangeLight Health today to receive a second opinion from a top U.S.-based lung cancer expert.
据2018年国际癌症数据统计，肺癌是中国最常见的癌症，占全部癌症类型的18.1%；在美国则是第二常见的癌症，占10.7% (Cancer Communications, 2019) 。过去三年里，很多新抗癌药物在中国上市，包括阿法替尼，奥希替尼，艾乐替尼等 ( National Medical Products Administration, 2020) 。治疗手段的增多亦使中美两国的官方癌症临床指南不断更新。本文将比较美国National Comprehensive Cancer Network (NCCN)和中国临床肿瘤学会的临床指南 (CSCO)进行比较，并着重介绍两国指南中对晚期非小细胞肺癌的药物推荐上的不同。
决定肺癌治疗方案的第一步，是确认肺癌的类型。中美两国肺癌的基本检测包括组织学分型与生物标志物分型。组织学检测可以告诉我们病变的细胞类型。在非小细胞肺癌中，三种主要的类型分别是腺癌、鳞状细胞肺癌和大细胞肺癌。而生物标志物分型则揭示了癌细胞的突变类型。在检测腺癌和大细胞肺癌时，两国指南推荐的生物标志物检测包括EGFR、 ROS1、 ALK和BRAF。在美国，PD-L1检测被推荐用于所有类型的肺癌(NCCN, 2020)；然而，在中国，仅推荐用于鳞癌肺癌(CSCO, 2020)。
EGFR、ROS1、 ALK和BRA是不同类型的细胞蛋白质。这些蛋白质的突变会导致癌细胞快速形成。一种被称为酪氨酸激酶抑制剂 (TKI）的药物可以阻止它们向癌细胞传达快速复制的信号，从而减缓癌细胞的增长 ( NCCN, 2020 )。癌细胞上的PD-L1可以保护癌细胞不被免疫系统杀死。免疫疗法以癌细胞上的免疫细胞或PD-L1为靶点，促进免疫系统杀死癌细胞 ( Nature Review, 2019)
EGFR是一种导致细胞生长异常的基因突变。研究显示，中国48%的肺癌患者有EGFR基因突变，而美国只有23%的肺癌患者有EGFR基因突变 ( American Journal of Cancer Research, 2015 )。然而，根据国家统计数据显示，中国只有9.6%的非小细胞肺癌患者检测了EGFR突变 ( Journal of Thoracic Oncology, 2016) 。美国NCCN临床指南推荐的5个高优先级别药物是：奥希替尼，厄洛替尼，阿法替你，吉非替尼和达科米替尼 ( NCCN, 2020 )。这五个药均已在中国上市，并且作为一线药物使用。除此之外，国产药物埃克替尼也在中国上市，并被批准作为转移性非小细胞肺癌的额外一线药物使用 ( CSCO, 2020 )
美国NCCN指南推荐用于治疗ALK融合阳性肺癌的一线治疗方案包括艾乐替尼 (首选）、布加替尼、色瑞替尼和克唑替尼。劳拉替尼在美国被推荐为二线药物 ( NCCN, 2020) 。在中国，克唑替尼是此前唯一一个被批准使用于ALK重排的TKI。2018年，艾乐替尼也被批准并推荐为一线治疗，色瑞替尼则作为二线药物被允许用于ALK融合阳性肺癌。劳拉替尼和布加替尼仍未在中国上市。国产药物安罗替尼于2018年研发并作为晚期非小细胞肺癌的三线药物使用 ( CSCO, 2020; National Medical Products Administration, 2020 )
在美国，克唑替尼和色瑞替尼是ROS1融合阳性肺癌的一线药物，二线药物为劳拉替尼 ( NCCN, 2020) 。而在中国，克唑替尼是唯一获批作为ROS1融合阳性肺癌线治疗的TKI。截至2020年9月，ROS1抑制剂恩曲替尼还未在中国获批。尽管恩曲替尼仍未在中国上市，但已被中国临床肿瘤学会指南列为ROS1融合阳性肺癌的一线治疗 ( CSCO, 2020; National Medical Products Administration, 2020 )
Based on 2018 global cancer statistics, lung cancer is the most common cancer in China, accounting for 18.1% of total cancer cases, while in the United States it is ranked second, with a 10.7% incidence rate (Cancer Communications, 2019) . Over the last three years, many new anticancer medications have been approved in China, such as afatinib, osimertinib, and alectinib( National Medical Products Administration, 2020) As more treatment options become available, the official cancer guidelines both in the U.S and in China are constantly changing. This article will focus on the differences in treatment guidelines in metastatic non-small cell lung cancer (NSCLC). The guidelines discussed are the National Comprehensive Cancer Network (NCCN) in the United States and Chinese Society of Clinical Oncology (CSCO) in China.
To determine the treatment for lung cancer, it is critical to first know the histologic type of lung cancer. In both countries, histologic typing and biomarker typing are used. Histologic typing tells where the cancer originates. In NSCLC, the three major types are adenocarcinoma, squamous cell lung cancer, and large cell lung cancer. Biomarker testing, on the other hand, reveals the type of mutations in the cancer cells. In adenocarcinoma and large cell lung cancer, biomarker testing recommended by both guidelines include EGFR, ROS1, ALK, and BRAF. PD-L1 testing is recommended in all types of lung cancer in the United States (NCCN, 2020) , however, in China, it is recommended only in squamous cell lung cancer (CSCO, 2020).
EGFR, ROS1, ALK and BRAF are all different types of cell proteins. Mutations of these proteins can lead to more rapid formation of cancer cells. A class of drugs called tyrosine kinase inhibitors (TKI) can stop them from sending signals to replicate cancer cells, thus de-accelerating the cancer’s growth ( NCCN, 2020 ) PD-L1 on cancer cells protects cancer cells from being killed by the immune system. Immunotherapy targets immune cells or PD-L1 on cancer cells to boost the immune system to kill cancer cells ( Nature Review, 2019)
Overactive EGFR Mutation:
EGFR mutation is a genetic mutation that results in abnormal cell growth. Studies showed that 48% of patients with lung cancer in China have EGFR gene mutation, compared to 23% of patients with EGFR mutation in America ( American Journal of Cancer Research, 2015 ). However, national survey data showed that only 9.6% of NSCLC patients in China were tested for EGFR mutation ( Journal of Thoracic Oncology, 2016) . The five most preferred medications recommended by U.S. NCCN guidelines are osimertinib, erlotinib, afatinib, gefitinib and dacomitinib ( NCCN, 2020 ). These five medications are all in the market in China and recommended by CSCO as first-line options. Apart from these medications, icotinib was developed in China and approved for metastatic NSCLC as an additional first-line therapy ( CSCO, 2020 )
First-line treatment options recommended by U.S. NCCN guidelines include alectinib (preferred), brigatinib, ceritinib, and crizotinib. Lorlatinib is recommended as a next-line option in the United States ( NCCN, 2020) . In China, crizotinib was previously the only TKI approved for the ALK mutation. In 2018, however, alectinib was approved and recommended as first-line therapy and ceritinib is now recommended as a second-line therapy. Lorlatinib and brigatinib are not on the market in China. Anlotinib was developed and approved in 2018 as a third-line therapy for metastatic NSCLC in China ( CSCO, 2020; National Medical Products Administration, 2020 )
Crizotinib and ceritinib are recommended as first-line therapies in the United States. The next-line therapy is lorlatinib ( NCCN, 2020) . While in China, crizotinib is the only TKI approved as a first-line treatment for ROS1 rearrangement. The ROS1 inhibitor entrectinib has not been approved in China as of 9/2020. That said, although entrectinib is not on the market in China, it is listed as a first-line therapy option for ROS1 rearrangement by China’s CSCO guidelines ( CSCO, 2020; National Medical Products Administration, 2020 )
Looking to learn more about different lung cancer treatment options available in China and in the United States? Reach out to RangeLight Health for a personalized second opinion from a top U.S.-based lung cancer specialist today.
在过去，改良根治性乳房切除术(一种切除乳房的外科手术)是乳腺癌的主要治疗方法 (Medscape 2019) 。随着研究对乳腺癌机理的不断深入，更新和更先进的治疗手段得以发展。如今，针对乳腺癌患者的靶向治疗有了显著的进展，保乳术也更加常见。
医生需要对乳腺癌细胞中的三种蛋白质进行检测，以确定正确的治疗方案：雌激素受体(ER)、黄体酮受体(PR)和人类表皮生长因子受体2 (HER2)。检测的重要性在于了解患者对这些受体的检测结果是阳性还是阴性，以确定对乳腺癌的治疗方案选择 (American Cancer Society, 2019) 。
ER和PR被称为激素受体。如果病人的检测出ER阳性或是PR阳性，代表这个病人的癌细胞是由这些激素喂养。内分泌疗法通过降低激素水平来减缓乳腺癌的进展 ( Mayo Clinic, 2019 )。HER2是一种能够促进癌细胞生长的受体。HER2阳性患者的癌细胞生长得更快，向大脑扩散的风险也更高。然而幸运的是，靶向治疗对这类癌症更有效果。研究者们致力于研发能够穿过血脑屏障的抗HER2药物。2020年4月，美国FDA批准了一种名为Trodelvy®的新药 ( National Cancer Institute, 2020) 。这个药可以和Herceptin® (trastuzumab)与Xeloda® (capecitabine)联合使用，用于治疗不能通过手术切除的HER2阳性乳腺癌或转移性乳腺癌 (National Institutes of Health, 2020) 。一项双盲临床试验表明，添加Tukysa®可以在不进一步恶化的情况下提高癌症扩散到大脑的妇女的生存率24.9% (N Engl J Med, 2020)。
乳腺癌的一种单独亚型被称为三阴乳腺癌，三阴代表以上三种蛋白质检测均呈阴性。由于三阴性乳腺癌对激素治疗或抗HER2治疗没有反应，因此更难治疗 ( National Cancer Institute, 2020 )。2020年4月，FDA通过了名为Trodelvy® (sacituzumab govitecan-hziy)的新药，用于治疗至少两种治疗手段失败的转移性三阴乳腺癌患者 ( JNational Institutes of Health, 2020) 。与以快速生长的细胞为靶点的传统化疗不同，这种药物将化疗直接送到癌细胞。基于转移性疾病的双盲临床试验中，Trodelvy®被证明对三分之一的患者中起效，治疗对病人起效时间的中位数为7.7个月 ( N Engl J Med, 2019 )。
Historically, modified radical mastectomy, a surgical removal of the breast, was the primary treatment of breast cancer (Medscape 2019) . However, as researchers learned about the science behind breast cancer, newer and more advanced treatments were developed. Today, there is significant research in targeted therapies for patients with breast cancer and breast conservation is much more common.
In breast cancer cells, there are three proteins that need to be tested for doctors to decide the right course of treatment: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is important to know if a patient tests positive or negative for these receptors to determine the appropriate treatment for breast cancer (American Cancer Society, 2019) .
ER and PR are known as hormone receptors. If a patient is ER positive or PR positive, this means that the cancer cells in this patient are fed by these hormones. Endocrine therapy decreases hormone levels to slow the progression of breast cancer ( Mayo Clinic, 2019 ). HER2 is a receptor that can promote the growth of cancer cells. In HER2 positive patients, cancer cells grow more rapidly and are at a higher risk of spreading to the brain. Fortunately, however, this type of cancer is more sensitive to targeted therapy. Researchers have focused on developing anti-HER2 medications that are able to cross the blood brain barrier. The FDA approved a new drug called Tukysa® (tucatinib) in April 2020 ( National Cancer Institute, 2020) . It was approved to be used in combination with Herceptin® (trastuzumab) and Xeloda® (capecitabine) in HER2 positive breast cancer that cannot be removed by surgery or in metastatic breast cancer (National Institutes of Health, 2020) . A double-blind clinical trial has shown that the addition of Tukysa® improves the survival in women with cancer spreading to the brain by 24.9% in one year without the cancer further progressing (N Engl J Med, 2020).
A separate subtype is called triple-negative breast cancer, which means that the patient tests negative for all three proteins. This is harder to treat because triple-negative breast cancer does not respond to hormone therapy or anti-HER2 therapy ( National Cancer Institute, 2020 ). A new drug Trodelvy® (sacituzumab govitecan-hziy) was approved by FDA in April 2020 to treat patients with metastatic triple-negative breast cancer, who have failed at least 2 other treatments ( JNational Institutes of Health, 2020) . Unlike traditional chemotherapy that targets rapid-growing cells, this medication delivers the chemotherapy directly to cancer cells. Based on a double-blind clinical trial for metastatic disease, it was shown to be effective in one third of patients. The median duration of reaction, which means the length of time that the patient is responsive to the treatment, is 7.7 months while on Trodelvy® ( N Engl J Med, 2019 )。
If you are interested in learning more about treatment options for breast cancer and new therapies, please contact RangeLight Health to set up a consultation with an expert U.S.-based oncologist.
结肠直肠癌 (包含肠癌与直肠癌）是一种下消化道恶性肿瘤。它来源于结直肠内壁息肉伴随时间推移而逐步形成的癌变。2014年，中国约有37万新确诊结肠直肠癌患者。结肠直肠癌的发病率占男性癌症发病率的第四位，女性癌症发病率的第三位 (Global Health Journal, 2018)
结肠直肠癌的治疗方案取决于很多因素：对于肿瘤还未扩散到周围组织或淋巴结的0期和1期的癌症患者，手术是标准治疗；对癌症中后期的病人，其治疗方案需结合病人整体健康状况与癌症分期。这其中可能会包含放化疗、手术、局部治疗、免疫疗法或靶向治疗 (American Cancer Society, 2020) 。
免疫疗法正如其名，系利用病人本身的免疫系统来对抗癌症。不同于将健康细胞与癌症细胞一起杀死的传统放化疗，免疫疗法尝试精准打击癌症细胞。好比导弹，免疫疗法将健康的快速分裂细胞排除在打击目标外。因此，免疫疗法相比传统放化疗，脱发可能性更小，副作用更能令人接受 (Nature Review, 2019)。
现阶段市面上有三种针对结肠直肠癌的免疫疗法：可瑞达® (帕博利珠单抗)、欧狄沃 (纳武利尤单抗）和 Yervoy® (伊匹木单抗）。可瑞达® 与欧狄沃®都作用于PD-1蛋白质。这种蛋白质如同一把“锁”，存在于免疫细胞T细胞上。当癌症细胞上的“钥匙” PD-L1 蛋白将T细胞上的“锁”锁上，癌症细胞就可以免于T细胞的攻击。可瑞达® 和欧狄沃®如同一层保护屏障保护着T细胞。这样，T细胞就可以自由攻击癌细胞而不被锁住 ( Nature Review, 2019 )。
Yervoy®是美国FDA于2018年批准的最新的直肠结肠癌免疫疗法药物。它与欧狄沃联用，治疗高度微卫星不稳定或DNA错配修复功能缺陷的癌症病人 (National Cancer Institute, 2018) 。不同于可瑞达® 与欧狄沃®，Yervoy®抑制了另一种叫做CTLA-4的蛋白质。在T细胞上的CTLA-4蛋白如同一个开关，开关闭合时，癌细胞便能逃脱T细胞的制裁。Yervoy®打开了这个开关，促进了病人对癌症细胞的免疫反应 (Nature Review, 2019)。
Colorectal cancer, including bowel cancer and rectal cancer, is a type of cancer involving the lower intestinal tract. It begins with a growth or polyp on the inner wall of the colon and progresses to cancer as time goes on. In 2014, there were an estimated 370,000 new colorectal cancer cases in China. It is the third most common cancer among women and the fourth most common cancer among men in China (Global Health Journal, 2018)
The treatment plan for colon cancer depends on a variety of factors. For stage 0 and 1 cases, the cancer has not spread outside into nearby tissue or lymph nodes; therefore, surgery is the standard treatment. With more advanced disease, chemotherapy, radiation, immunotherapy, surgery, local therapies, or targeted therapy may be needed based on the patient’s health status and stage. (American Cancer Society, 2020) 。
Immunotherapy, as its name implies, works by using the patient’s immune system to fight cancer. Unlike traditional chemotherapy and radiation therapy where healthy cells are killed alongside cancerous cells, immunotherapy tries to aim specifically at the cancer cells like a guided missile. As this therapy attempts to spare the healthy, rapid growing cells, immunotherapy has the advantage of fewer unwanted side effects such as hair loss (Nature Review, 2019)。
There are currently three immunotherapy medications on the market for colorectal cancer, Keytruda® (pembrolizumab), Opdivo®(nivolumab), and Yervoy®(ipilimumab). Keytruda® and Opdivo® target a protein called PD-1 on the immune system cells, T cells. PD-1 acts as a lock on the T cell. Once the lock on T cells gets locked by the “key” protein PD-L1 located on the cancer cell, the cancer cell can escape from being killed by T cells. Keytruda® and Opidivo® act as shield protections to protect the lock on the T cells. In this case, T cells will not be locked by cancer cells and can kill the cancer cells more easily (Nature Review, 2019 )。
Yervoy® is the newest immunotherapy approved by the FDA for colorectal cancer in 2018. In patients with microsatellite instability-high or mismatch repair deficient cancers, it is used along with Opdivo® ( National Cancer Institute, 2018) . Unlike Keytruda® and Opdivo® which block the protein PD-1, Yervoy® works by blocking a different protein, CTLA-4. CTLA-4 protein acts as an additional “off” switch on T cells to keep T cells from killing cancer cells. By blocking the “off” switch CTLA-4, Yervoy® boosts a patient's immune response to the cancer cells (Nature Review, 2019).
There are a number of clinical trials focused on colon cancer that utilize a variety of different treatment methods, such as monospecific and bispecific antibodies, cellular therapies, and vaccines (Nature Review, 2019)。 . At RangeLight Health, we understand that it can be overwhelming to understand the relative nuances and intricacies of new colon cancer treatments. We are here to help you manage this process. Contact RangeLight Health today，to speak with a top U.S.-based oncologist and learn more about new colon cancer treatment options.
乳腺癌是中国女性中最常见的癌症，也是美国第二大最常见的癌症 (CA Cancer J Clin, 2018; American Cancer Society, 2020)。 在过去的几十年中，有许多新药物被用于来治疗晚期乳腺癌。越来越多的治疗选择也让中国和美国的治疗指南也在不断变化。本文将重点介绍晚期乳腺癌的治疗方案，并比较美国国家综合癌症网络(NCCN)指南与中国临床肿瘤学会（CSCO）指南之间的差异。
美国NCCN和中国CSCO指南均建议使用化疗和HER2靶向治疗作为晚期HER2阳性乳腺癌患者的一线治疗。在美国，首选的治疗方案是帕妥珠单抗，曲妥珠单抗加紫杉烷（多西他赛或紫杉醇）。除此之外，中国指南将帕妥珠单抗，卡培他滨加紫杉烷作为另一种首选治疗方案。其他药物选择包括酪氨酸激酶抑制剂（TKIs）。拉帕替尼和那拉替尼是在美国治疗HER2阳性乳腺癌的推荐TKIs (NCCN, 2020; CSCO, 2020 )。 在中国，虽然拉帕替尼和那拉替尼都已上市，但CSCO指南仅推荐拉帕替尼用于治疗HER2阳性乳腺癌。 2018年，中国开发了一种名为吡咯替尼的TKI。如果曲妥珠单抗对患者没有效果，那么中国CSCO指南推荐吡罗替尼加卡培他滨作为下一线治疗方法 (CSCO, 2020)。
中美两国指南均建议采用内激素治疗±细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂。两国推荐的激素治疗药物包括芳香化酶抑制剂（阿那曲唑、依西美坦和来曲唑）、雌激素受体下调剂（氟维司汀）和选择性雌激素受体调节剂（他莫昔芬和托瑞米芬）。这些药物可以通过不同的机制阻止雌激素与雌激素受体的结合。 CDK4/6抑制剂可以减缓癌细胞生长。美国指南推荐的CDK4/6抑制剂包括帕博西尼（Ibrance）、ribociclib（Kisqali）和abemaciclib（Verzenio）。截至2020年9月，帕博西尼是唯一在中国获得批准上市的CDK4/6抑制剂。中美之间的另一个治疗上的差异是组蛋白脱乙酰基酶（HDAC）抑制剂的使用。 HDAC抑制剂通过抑制DNA修复来阻止癌细胞的生长并刺激癌细胞死亡。这类药物仅在中国推荐用于激素受体阳性的乳腺癌的二线治疗使用。CSCO指南推荐HDAC抑制剂与芳香酶抑制剂联合使用 (NCCN, 2020; CSCO, 2020)。
基因突变是引发癌症的重要因素。美国推荐乳腺癌需要进行的基因检测包括BRCA1和BRCA2。美国NCCN指南推荐用于治疗BRCA1和BRCA2突变阳性的乳腺癌患者的药物包括奥拉帕尼（Lynparza）和他拉唑帕尼（Talzenna） (NCCN, 2020;)。 奥拉帕尼和他拉唑帕尼是口服靶向药物，可通过干扰DNA转录和修复来抑制肿瘤细胞的生长，被FDA批准用于先前接受过化疗和激素疗法的患者 (Lynparza®, 2020; Talzenna®, 2018)。 在中国，CSCO并未正式推荐奥拉帕尼用于BRCA1和BRCA2突变阳性的乳腺癌患者，但该药的疗效在指南中有所提及 (NCCN, 2020; CSCO, 2020)。 截至2020年9月，他拉唑帕尼在中国仍未获得批准 (National Medical Products Administration, 2020)。
想要了解更多中美两国不同的乳腺癌治疗方案? 欢迎咨询 领昱医疗 ，以获取更多自美国顶级乳腺癌专家的二次诊疗意见。
Breast cancer is the most common cancer in women in China and the second most common cancer in the United States (CA Cancer J Clin, 2018; American Cancer Society, 2020) . Over the past decades, many medications have been developed to treat metastatic breast cancer. With more and more treatment options available, guidelines in China and in the United States are constantly changing. This article will focus on treatment options in metastatic breast cancer, comparing the differences between the National Comprehensive Cancer Network (NCCN) guidelines in the United States and Chinese Society of Clinical Oncology (CSCO) guidelines in China.
Both the U.S. NCCN and China CSCO guidelines recommend using chemotherapy and HER2 targeted therapy as first-line treatment for metastatic HER2 positive patients. The preferred option in the United States is pertuzumab, trastuzumab plus taxane (docetaxel or paclitaxel). In addition to this regimen, pertuzumab, capecitabine plus taxane is another preferred treatment plan in China. Other treatment options include tyrosine kinase inhibitors (TKIs). Lapatinib and neratinib are the recommended TKIs to treat HER2 positive breast cancer in the United States (NCCN, 2020; CSCO, 2020 ). While in China, both lapatinib and neratinib are on the market, only lapatinib is recommended by CSCO guidelines in treating HER2 positive breast cancer. In 2018, China developed another TKI named pyrotinib. Pyrotinib plus capecitabine is the preferred treatment in China if the patient has not responded to trastuzumab (CSCO, 2020)。
Hormone receptor positive:
Endocrine therapy with or without a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is recommended by both guidelines. Endocrine therapies recommended in both countries include aromatase inhibitors (anastrozole, exemestane, and letrozole), estrogen receptor down-regulator (fulvestrant) and selective estrogen receptor modulator (tamoxifen and toremifene). These medications prevent estrogen from binding to the estrogen receptors through different mechanisms. CDK4/6 inhibitors are a class of drugs that can slow the growth of cancer cells. CDK4/6 inhibitors recommended in the United States include palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). While in China, palbociclib is the only approved CDK4/6 inhibitor as of September 2020. Another difference between the treatment in China and the United States is the use of Histone deacetylase (HDAC) inhibitors. HDAC inhibitors stop the growth of cancer cells and stimulate cancer cell death by inhibiting DNA repair. This class of drugs is recommended only in China to treat hormone receptor positive breast cancer as a second-line therapy. It is recommended in combination with aromatase inhibitors by CSCO guidelines (NCCN, 2020; CSCO, 2020)。
Gene mutation is an important factor in cancer. Genetic testing recommended in the United States include BRCA1 and BRCA2. Drugs recommended by U.S. NCCN guidelines to treat breast cancer patients with BRCA1 and BRCA2 mutations are olaparib (Lynparza) and talazoparib (Talzenna) (NCCN, 2020;)。 . Olaparib and talazoparib are oral targeted therapies that inhibit tumor cell growth by interfering with DNA transcription and repair. They are approved for patients who have previously received chemotherapy or endocrine therapy (Lynparza®, 2020; Talzenna®, 2018)。 . While, in China, CSCO does not officially recommend olaparib for breast cancer patients with BRCA1 and BRCA2 mutations, the drug’s efficacy is mentioned in the guidelines (NCCN, 2020; CSCO, 2020)。 . Talazoparib has not been approved in China as of September 2020 (National Medical Products Administration, 2020)。
Want to learn more about different breast cancer treatment options available in China and in the United States? Contact RangeLight Health for a personalized second opinion from a top U.S.-based breast cancer specialist today.
在中国，结直肠癌是女性第三常见癌症、男性第四常见癌症。 (Global Health Journal, 2018) 。手术是还未扩散至附近的组织或淋巴结里的早期结直肠癌（如0期或1期）的标准治疗方案 (American Cancer Society, 2020) 。不幸的是，中国大多数患者被诊断为结直肠癌的晚期，因为其症状往往不明显，在早期可能难以察觉。事实上，许多结肠癌患者可能只有轻微的症状，直到癌症严重恶化。
癌症起始于人体内一个或几个基因突变。DNA错配修复缺陷是结直肠癌的常见原因之一。DNA错配修复是人体内的一种用于识别并修复基因突变的系统。DNA错配修复系统缺陷会使体内的突变修复系统失活，从而导致结直肠癌等多种疾病 (Human Molecular Genetics, 2001) 。
美国正在进行很多针对结直肠癌治疗的临床试验。在一项临床试验里，美国国家癌症研究所正在研究标准化疗与一种名为Tencentrq®（阿特珠单抗）的免疫治疗药物联合治疗DNA错配修复缺陷的3期结肠癌患者的疗效。化疗通过不同的方式以阻止肿瘤细胞的增长，与此同时Tencentriq®（阿特珠单抗）帮助身体免疫系统攻击癌症。这项三期试验正在研究联合用药是否比单独化疗更加有效。该试验预计于2020年12月完成，预估有700名患者报名参与 (Clinicaltrials.gov, 2020)。
近期研究显示，48.9%的中国结直肠癌病人检测到基因突变。 KRAS基因是中国结直肠癌患者中最常见的基因突变 (Clinicaltrials.gov, 2020) 。它负责在人体中制造一种特殊的蛋白质，作为细胞生长和分裂的开关。这种基因的突变可能会永久地开启这一开关。因此，KRAS基因的突变可能导致侵袭性和更难治疗的结肠癌病例 (Journal of Medicine and Life, 2014)。
In China, colorectal cancer is the third most common cancer among women and the fourth most common cancer among men (Global Health Journal, 2018) . Surgery is the standard treatment for early-stage colorectal cancer from stage 0 and stage 1, when the cancer has not spread into nearby tissue or lymph nodes (American Cancer Society, 2020) .Unfortunately, the majority of patients in China are diagnosed at advanced stages of colorectal cancer since the symptoms are often subtle and may be difficult to notice in early stages. In fact, many colon cancer patients may only have mild symptoms until the cancer has become significantly advanced.
often subtle and may be difficult to notice in early stages. In fact, many colon cancer patients may only have mild symptoms until the cancer has become significantly advanced. Cancer starts with one or several gene mutations in the human body. Deficient DNA mismatch repair is one of the common causes of colorectal cancer. DNA mismatch repair is a system in the body to identify and fix DNA mutations. Deficient DNA mismatch repair will deactivate the mutation repair system in the body and can lead to multiple diseases, including colon cancer (Human Molecular Genetics, 2001) 。
There are a number of clinical trials focused on new colon cancer treatment and therapies. In one clinical trial, the National Cancer Institute is investigating the efficacy of the combination of standard chemotherapy with an immunotherapy drug called Tencentriq® (atezolizumab) in stage 3 colon cancer patients with DNA mismatch repair deficiency. Chemotherapy works in different ways to stop tumor cell growth, while Tencentriq® helps the body’s immune system attack cancer. This phase 3 trial is investigating if the combination involving immunotherapy is more effective than chemotherapy alone. It is estimated 700 participants have enrolled and expected to be completed in December 2020 (Clinicaltrials.gov, 2020)。
A recent study revealed that 48.9% of Chinese colorectal patients were detected with gene mutations. The KRAS gene is the most common gene mutation among all Chinese colorectal cancer patients (Clinicaltrials.gov, 2020) . It is responsible for making a specific protein in the human body, which functions as a switch for cell growth and division. Mutation in this gene may permanently turn on the switch. Therefore, the mutated KRAS gene may lead to colon cancer cases that are aggressive and more difficult to treat (Journal of Medicine and Life, 2014)。
Onvansertib is one of the investigational drugs targeted towards patients who have unresectable metastatic colorectal cancer with a KRAS mutation. The ongoing phase 1b/2 trial is evaluating the safety and efficacy of onvansertib in combination with chemotherapy and targeted therapy as the second preferable treatment regimen for patients (Clinicaltrials.gov, 2020) . On May 28, 2020, FDA granted Fast Track designation to onvansertib, thus expediting the drug’s review (Cardiff Oncology, 2020)。
Want to learn more about colorectal clinical trials and new colon cancer treatments in the U.S.? Contact RangeLight Health today to receive a second opinion from a top U.S.-based colorectal cancer expert.
针对不同的基因突变，科学家研发了不同的对症疗法。NCCN指南推荐了三种靶向药物用于治疗胃癌，分别是赫赛汀®（曲妥珠单抗），Cyramza®（雷莫芦单抗），可瑞达®（帕博利珠单抗） (NCCN, 2019) 。赫赛汀®被推荐为HER2过度表达晚期胃癌和胃食管结合部癌的一线药物 (Herceptin® FDA Label, 2010) 。Cyramza®的作用部位是一种叫血管内皮生长因子受体2的蛋白质，被批准用于曾接受过化疗的胃癌病人的治疗 (Cyramza® FDA Label, 2014) 。可瑞达®作用于MSI-H/dMMR和PD-1靶点，作为MSI-H/dMMR与PD-L1阳性胃癌患者的后续治疗使用 (NCCN, 2019) 。除此之外，NCCN推荐NTRK基因融合检测阳性的胃癌患者使用Rozlytrek ® （恩曲替尼）或Vitrakvi® (拉罗替尼） (Rozlytrek FDA Label, 2019; Vitrakvi FDA Label, 2020)
虽然市面上有越来越多的靶向药物和免疫疗法可供选择，但化疗由于其高效的特质，依然是胃癌标准治疗中重要的一部分。科学家们正在积极研发能更有效地对抗癌症的化疗药物，例如2019年在美国上市的化疗药物朗斯弗®（曲氟尿苷替匹嘧啶），它可以用于已经服用过至少两种化疗药物的晚期胃癌或者胃食管结合部癌病人 (National Institutes of Health, 2019) 。一项双盲随机对照临床试验显示，服用朗斯弗®的病人的中位存活期为5.7个月 (The Lancet Oncology, 2018)。
Stomach cancer is the second most common cancer in men and the fifth most common cancer in women in China (Cancer Communications, 2019) . Standard treatment in stage 0-3 stomach cancer involves surgery. In stomach cancer that has metastasized, chemotherapy is used as the main treatment to slow cancer growth and prolong patients’ lives (American Cancer Society, 2019) .
Additional treatments with proven efficacy have been developed to achieve better outcomes. To decide the appropriate treatment for stomach cancer, biomarker testing is recommended by the National Comprehensive Cancer Network (NCCN). Biomarker testing helps in making treatment decisions because it indicates the mutation that contributed to the cancer. In stomach cancer, the recommended biomarkers to be tested are: human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and Microsatellite instability high/deficient mismatch repair (MSI-H/dMMR).
Various therapies have been designed to target these mutations. Three targeted therapies recommended by NCCN to treat stomach cancer include Herceptin® (trastuzumab), Cyramza® (ramucirumab), and Keytruda® (pembrolizumab) (NCCN, 2019) . Herceptin® is a preferred first-line therapy approved in HER2-overexpressing metastatic stomach cancer and gastroesophageal junction (GEJ) cancer patients (Herceptin® FDA Label, 2010) . Cyramza® targets a protein named vascular endothelial growth factor receptor (VEGFR). It is approved to be used in stomach cancer patients who have previously received chemotherapy (Cyramza® FDA Label, 2014) . Keytruda®, which targets MSI-H/dMMR and PD-1, is a subsequent therapy for both MSI-H/dMMR tumors and gastric cancer with PD-L1 expression (NCCN, 2019) . In NTRK-gene fusion positive stomach cancer patients, Rozlytrek ® (entrectinib) or Vitrakvi® (larotrectinib) are recommended by the NCCN (Rozlytrek FDA Label, 2019; Vitrakvi FDA Label, 2020) .
While there are now more targeted therapies and immunotherapies developed to treat cancers, chemotherapy remains a part of standard treatment for stomach cancers due to its efficacy. Scientists are actively working on developing more advanced chemotherapy to help individuals fight cancers. For example, Lonsurf® (tipiracil/trifluridine) was approved in 2019 to treat metastatic gastric cancer and gastroesophageal junction (GEJ) cancer in patients who had been treated with at least two chemotherapies previously (National Institutes of Health, 2019) . A double-blinded randomized clinical trial has shown a median survival of 5.7 months when taking Lonsurf® (The Lancet Oncology, 2018) .
Looking to learn more about new stomach cancer treatments and therapies? Contact RangeLight Health today to receive a personalized second opinion from an U.S.-based expert cancer specialist.
肝细胞性肝癌（HCC）是全球范围内最常见的肝癌类型 (Nature Reviews Gastroenterology & Hepatology, 2019) ，通常伴有慢性肝病和肝硬化在中国，乙型肝炎和丙型肝炎是最为常见的病因；在美国，最常见的病因则是肥胖导致的非酒精性脂肪肝 (Medscape, 2020) 。相较于其他国家，肝细胞性肝癌在中国更为常见。每年全球有超过75.6万例患者被确诊为肝细胞性肝癌，其中有超过35.3万例的中国病例 (Roche, 2020) 。早期肝癌的首选治疗方案是手术治疗，例如肝部分切除术甚至肝移植。另一种选择是局部治疗，例如经皮消融术，利用无线电波或微波来摧毁癌细胞。然而对于肝癌晚期患者来说，接受包括药物治疗的全身治疗是更加理想的选择 (American Cancer Society, 2019) 。本文将着重介绍无法进行手术或放疗的晚期肝癌患者的药物选择。
美国国家综合癌症网络(NCCN)指南推荐，晚期肝癌患者首选疗法包括Nexavar® (索拉非尼), Lenvima® (乐伐替尼)或者阿特珠单抗联合贝伐珠单抗 (NCCN, 2020) 。Nexavar® 和Lenvima®属于一类被称为酪氨酸激酶抑制剂的靶向治疗。靶向治疗攻击那些促进癌细胞生长的特定基因或蛋白质，如今已是癌症治疗方向的重点研究对象之一 (American Society of Clinical Oncology, 2020) 。在过去的很多年间，Nexavar®一直是肝细胞性肝癌的唯一靶向疗法。然而，在过去的三年里，已经有几种靶向治疗被批准用于治疗肝癌，比如Stivarga® (瑞戈菲尼) 和Cabometyx® (卡博替尼) (National Cancer Institute, 2020) 。FDA允许这些靶向药物用于曾接受过 Nexavar®治疗的肝癌患者 (Stivarga® FDA Label, 2017; Cabometyx® FDA Label, 2019)
阿特珠单抗联合贝伐珠单抗是肝癌的另一个一线疗法，于2020年5月被FDA批准 (FDA, 2020) 。贝伐珠单抗属于单克隆抗体，它可以防止癌细胞生成为自己提供养分的血管，从而放缓肝癌细胞的生长速度 (American Cancer Society, 2020) 。阿特珠单抗是一种免疫疗法药物，它通过刺激免疫系统杀死癌细胞，贝伐珠单抗需要和阿特珠单抗一起使用 (NCCN, 2020)) 。一个全球范围的临床试验显示，服用阿特珠单抗联合贝伐珠单抗的患者的一年存活率是67.2%，而服用Nexavar®的患者一年存活率为54.6% (N Engl J Med, 2020) 。2020年3月，另一个免疫疗法药物Opdivo® （纳武单抗）在美国得到FDA批准，用于之前服用过Nexavar®的肝癌患者的治疗 (FDA Label Opdivo®, 2020)
Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer worldwide (Nature Reviews Gastroenterology & Hepatology, 2019) . Usually, it occurs with chronic liver disease and cirrhosis. Prevalence of hepatitis B and C are major risk factors in China, while nonalcoholic fatty liver disease caused by obesity is the leading cause in the United States (Medscape, 2020) . HCC is more common in China than other countries. Annually, over 756,000 HCC cases are diagnosed worldwide, and more than 353,000 are diagnosed in China (Roche, 2020) rtial hepatectomy (partial removal of liver), otherwise the patient would be evaluated for liver transplantation. Another option is locoregional therapy, such as percutaneous ablation, which is a procedure that utilizes radio waves or microwaves to destroy the cancer. However, systemic treatment involving drug therapies is commonly utilized in advanced liver cancer (American Cancer Society, 2019) . This article will focus on medication therapies in patients who are not surgical or transplant candidates.
Therapies recommended by National Comprehensive Cancer Network (NCCN) to use first in advanced liver cancer are Nexavar® (sorafenib), Lenvima® (lenvatinib), or atezolizumab plus bevacizumab (NCCN, 2020) . Nexavar® and Lenvima® are a type of targeted therapy called kinase inhibitors. Targeted therapy, which attacks specific genes or proteins that help cancer cells grow, is one of the major focuses in research to treat cancer (American Society of Clinical Oncology, 2020) . Nexavar® had been the only targeted therapy to treat HCC for many years. In the last three years, however, several existing targeted therapies have been approved to treat liver cancer, including: Stivarga® (regorafenib) and Cabometyx® (cabozantinib) (National Cancer Institute, 2020) . These medications are approved to be used in liver cancer patients who have been previously treated with Nexavar® (Stivarga® FDA Label, 2017; Cabometyx® FDA Label, 2019)
Atezolizumab plus bevacizumab is another first-line therapy in liver cancer. It was approved by FDA in May 2020 (FDA, 2020) . Bevacizumab belongs to a class called monoclonal antibody. It slows the growth of cancer by preventing blood vessel formation (American Cancer Society, 2020) . This drug is used with the immunotherapy medication atezolizumab, which works by stimulating the immune system to kill cancer cells (NCCN, 2020)) . A global clinical trial has shown a one-year overall survival of 67.2% with atezolizumab plus bevacizumab and 54.6% with Nexavar® (N Engl J Med, 2020) . Another new immunotherapy approved in March 2020 to treat advanced liver cancer is Opdivo® (nivolumab). It is approved to be used in liver cancer patients who have been previously treated with Nexavar® (FDA Label Opdivo®, 2020)
Want to learn more about liver cancer treatments and new clinical trials? Contact RangeLight Health today to receive a personalized second opinion from a top U.S.-based cancer expert.
结肠癌是中国第四大常见癌症。如今快餐饮食和久坐不动的生活方式在中国越来越普遍，导致中国居民罹患结肠癌的风险与日俱增。因此，增加结直肠癌早期筛查和结直肠癌治疗方法的科普在临床上有着重要的意义 (Chin J Cancer Res, 2019) 。本文将重点讨论晚期结肠癌，并讨论中美之间的治疗指南有何不同。
美国使用的临床指南由美国 National Comprehensive Cancer Network（NCCN）发布，而中国使用的指南由中国临床肿瘤学会（CSCO）发布。决定结肠癌的治疗方案，首先需要进行生物标志物检测，来确认癌症中存在的突变。两项指南均建议测试微卫星不稳定性高/缺陷错配修复（MSI-H/dMMR）、KRAS/NRAS和BRAF基因检测 (NCCN, 2020; CSCO, 2020) 。除了在结肠癌中检测到的突变外，结肠癌的病灶部位对于治疗决策也很重要。例如，治疗左侧结直肠癌时，采用西妥昔单抗（Erbitux）的患者总体生存率比贝伐单抗（Avastin）更高。然而，在右侧结直肠癌治疗中，患者使用贝伐单抗的总体生存率更高 (JAMA Oncol, 2017) 。
美国NCCN和中国CSCO指南均推荐化疗或化疗联合靶向治疗作为首选治疗方案。首选的化疗方案包括：CAPEOX（卡培他滨+奥沙利铂）、FOLFOX（亚叶酸、氟尿嘧啶+奥沙利铂）和FOLFIRI（亚叶酸、氟尿嘧啶+伊立替康）。在这两个国家中均建议使用FOLFOX / FOLFIRI±西妥昔单抗来治疗无KRAS/NRAS突变的左侧结肠癌患者，并推荐所有患者使用CAPEOX/FOLFOX/FOLFIRI±贝伐单抗 (NCCN, 2020; CSCO, 2020) 。在美国，另一种最为推荐的一线靶向药物是帕尼单抗（Vectibix） (NCCN, 2020) 。截至2020年9月，该药尚未在中国获得批准 (National Medical Products Administration, 2020)) 。
dMMR/MSI-H型直肠癌患者可以考虑进行免疫治疗。美国NCCN指南推荐的选项包括Opdivo®（纳武单抗）、Keytruda®（帕博利珠单抗）和Yervoy®（ipilimumab） (NCCN, 2020) 。Opdivo®和Keytruda®自2018年开始均已在中国上市。截至2020年9月，Yervoy®尚未在中国获得批准 (National Medical Products Administration, 2020) 。在中国CSCO指南中，根据患者的意愿和严重程度，免疫治疗被列为转移性dMMR / MSI-H型直肠癌的可选方案；然而CSCO指南中未提及特定的免疫疗法药物选择 (CSCO, 2020) 。
Colorectal cancer is the fourth most common cancer in China. As more individuals in China adopt Westernized diets and sedentary lifestyles, they are put at higher risk for developing colon cancer. Therefore, it is important to increase early-screening and learn more about effective colorectal cancer treatment (Chin J Cancer Res, 2019) . This article will focus on metastatic colorectal cancer and speak to how the treatment guidelines differ between China and the United States.
The National Comprehensive Cancer Network (NCCN) publishes guidelines for the United States and the guidelines used in China are published by Chinese Society of Clinical Oncology (CSCO). To determine the treatment plan in metastatic colorectal cancer, biomarker testing is recommended to identify mutations present in the cancer. Both guidelines recommend testing microsatellite instability high/deficient mismatch repair (MSI-H/dMMR), KRAS/NRAS and BRAF genes (NCCN, 2020; CSCO, 2020) . Besides mutations detected in colorectal cancer, the location of the cancer is important to the treatment decision as well. For instance, it is found that chemotherapy with cetuximab (Erbitux) has improved the overall survival more significantly than bevacizumab (Avastin) in left-sided colorectal cancer. However, in right-sided colorectal cancer, bevacizumab has better survival outcomes (JAMA Oncol, 2017) .
Both U.S. NCCN and China CSCO guidelines recommend chemotherapy with or without a targeted therapy as the first choice. The preferred chemotherapy regimens include: CAPEOX (capecitabine plus oxaliplatin), FOLFOX (leucovorin, fluorouracil plus oxaliplatin), and FOLFIRI (leucovorin, fluorouracil plus irinotecan). FOLFOX/FOLFIRI with or without cetuximab is recommended in both countries to treat left-sided colorectal cancer patients with no KRAS/NRAS mutation, and CAPEOX/FOLFOX/FOLFIRI with or without bevacizumab in all patients (NCCN, 2020; CSCO, 2020) . Another targeted therapy recommended in the United States as the first line in left-sided colorectal cancer is panitumumab (Vectibix) (NCCN, 2020) . This drug has not been approved in China as of September 2020 (National Medical Products Administration, 2020)) .
Immunotherapy is recommended in patients with dMMR/MSI-H colorectal cancer. Options recommended by U.S.NCCN guidelines include Opdivo® (nivolumab), Keytruda® (pembrolizumab), and Yervoy® (ipilimumab) (NCCN, 2020) . Both Opdivo® and Keytruda® have been on the market in China since 2018. As of September 2020, Yervoy® has yet to be approved in China (National Medical Products Administration, 2020) . In Chinese CSCO guidelines, immunotherapy is listed as a possible consideration for metastatic dMMR/MSI-H colorectal cancer according to the patient's willingness and severity of cancer. However, no specific immunotherapy drug options were mentioned in CSCO guidelines (CSCO, 2020) .
Looking for more personalized information on colorectal cancer treatment options available in China and in the United States? Contact RangeLight Health for an expert second opinion from a top U.S.-based colorectal cancer specialist today.