强生新一代治疗前列腺癌新药Erleada(Apalutamide Tablets)获FDA批准， 可延长生存期超2年。
2018年2月19日讯，美国食品药品监督管理局(FDA)批准强生(Johnson & Johnson)旗下的杨森(Janssen)公司下一代雄激素受体抑制剂Erleada(apalutamide)，用于治疗非转移性去势抵抗性前列腺癌(NM-CRPC)患者。这些患者虽然在接受激素治疗，但肿瘤仍继续增长。值得一提的是，它是首个经FDA批准的用于非转移性去势抵抗性前列腺癌的疗法。

图片来源：Janssen Biotech, Inc

美国国立卫生研究院的国家癌症研究所(NCI)的数据显示，前列腺癌是美国第二大癌症类型，NCI估计2017年大约有161,360名男性被诊断患有前列腺癌，26,730人 死于疾病。，约10%至20%的前列腺癌病例是去势抵抗性的。其中16%在确诊为去势抵抗时没有发生转移。
FDA药物评估与研究中心血液学和肿瘤学产品办公室代理主任兼FDA肿瘤卓越中心主任Richard Pazdur博士对此表示，FDA在批准肿瘤药物时评估了多种测量药物作用的方法。此次批准是首个将无转移生存作为终点审批的药物，就是测量肿瘤没有扩散到身体其它部位的时间，或在治疗开始后直到死亡的时间。而Erleada在支持批准的试验中表现良好。
Erleida一款雄激素受体抑制剂，通过阻断雄激素来减缓肿瘤的生长。Erleadas的安全性和有效性基于1,207例非转移性，去势抵抗性前列腺癌患者的随机临床试验。试验中的患者接受Erleada或安慰剂，所有患者还接受激素治疗，使用促性腺激素释放激素(GnRH)或通过手术降低体内睾酮的数量。 结果显示，服用Erleada的患者的中位无转移生存期为40.5个月，而服用安慰剂的患者的中位无转移生存期为16.2个月。
Erleada的常见副作用包括疲劳，高血压(高血压)，皮疹，腹泻，恶心，体重减轻，关节疼痛(关节痛)，食欲下降，四肢骨折和肿胀(外周水肿)。严重副作用包括跌倒，骨折和癫痫发作。

ERLEADA™ (apalutamide), a Next-Generation Androgen Receptor Inhibitor, Granted U.S. FDA Approval for the Treatment of Patients with Non-Metastatic Castration-Resistant Prostate Cancer
•ERLEADA™ is the first FDA-approved therapy to treat patients with non-metastatic castration-resistant prostate cancer
•Approval is based on Phase 3 SPARTAN clinical trial data which showed ERLEADA™ decreased the risk of distant metastasis or death by 72 percent and improved median metastasis-free survival by more than two years
•The major efficacy outcome was supported by statistically significant improvements for secondary endpoints, including time to metastasis, progression-free survival, and time to symptomatic progression
Important Safety Information4
CONTRAINDICATIONS
Pregnancy - ERLEADA™ can cause fetal harm and potential loss of pregnancy.
WARNINGS AND PRECAUTIONS
Falls and Fractures - In the SPARTAN study, falls and fractures occurred in 16% and 12% of patients treated with ERLEADA™ compared to 9% and 7% treated with placebo respectively. Falls were not associated with loss of consciousness or seizure. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone targeted agents.
Seizure - In a randomized study (SPARTAN), two patients (0.2%) treated with ERLEADA™ experienced a seizure. Permanently discontinue ERLEADA™ in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA™. Advise patients of the risk of developing a seizure while receiving ERLEADA™ and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.
ADVERSE REACTIONS
Adverse Reactions - The most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
Laboratory Abnormalities
•Hematology: anemia ERLEADA™ 70% (Grade 3-4 0.4%) placebo 64% (Grade 3-4 0.5%) leukopenia ERLEADA™ 47% (Grade 3-4 0.3%) for, placebo 29% (Grades 3-4 0%), lymphopenia ERLEADA™ 41% (Grade 3-4 2%), placebo 21% (Grade 3-4 2%);
•Chemistry – hypercholesterolemia ERLEADA™ 76%(Grade3-4 0.1%), placebo 46% (Grade 3-4 0%); hypertriglycemia ERLEADA™ 70%(Grade 3-4 2%) Placebo 59% (0.8%); hypertriglyceridemia ERLEADA™ 67%(Grade 3-4 2%) placebo 49%(Grade 3-4 0.8%); Hyperkalemia ERLEADA™ 32%(Grade 3-4 2%) Placebo 22%(Grade 3-4 0.5%)
Rash - Rash was most commonly described as macular or maculo-papular. Adverse reactions were 24% with ERLEADA™ versus 6% with placebo. Grade 3 rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA™ treatment (5%) versus placebo (0.3%).
The onset of rash occurred at a median of 82 days. Rash resolved in 81% of patients within a median of 60 days (range: 2 to 709 days) from onset of rash. Four (4%) of patients treated with ERLEADA™ received systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with ERLEADA™.
Hypothyroidism - Hypothyroidism was reported for 8% of patients treated with ERLEADA™ and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA™ and 7% of patients treated with placebo. The median onset was Day 113. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.
Effect of Other Drugs on ERLEADA - Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary however, reduce the ERLEADA™ dose based on tolerability [see Dosage and Administration (2.2)].
DRUG INTERACTIONS
Effect of ERLEADA™ on Other Drugs – ERLEADA™ is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA™ with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA™ with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA™ and evaluate for loss of activity.
P-gp, BCRP or OATP1B1 substrates - Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA™ with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with ERLEADA™ and evaluate for loss of activity if medication is continued.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science.
参考资料：
FDA approves new treatment for non-metastatic, castration-resistant prostate cancer.
https://www.rxlist.com/erleada-drug.htm