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2019年肿瘤领域最受瞩目的会议——美国临床肿瘤学会年会（ASCO）——于美国芝加哥当地时间5月31日拉开帷幕。在会议第一天亮相的临床研究中，2项研究同期在线发表于《新英格兰医学杂志》（NEJM）。 其中，Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma由中国团队主导完成，这是2天之内中国团队再次登上NEJM（参见5月30日报道《2019首篇中国团队〈新英格兰医学杂志〉论著：蜱传播的新病毒》）。 该研究是由研究者发起的试验（IIT），其通讯作者中山大学附属肿瘤医院副院长、肿瘤防治中心放射治疗科马骏教授在ASCO大会上报告了这项多中心3期临床试验的主要结果。 我们在此发表两篇论著摘要的中文翻译，请读者继续关注我们在ASCO期间的相关报道。 鼻咽癌的吉西他滨联合顺铂诱导化疗 Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma 摘 要 背景 铂类同步放化疗是局部区域晚期鼻咽癌患者的标准治疗。加用吉西他滨联合顺铂诱导化疗在2期试验中显示出很有前景的疗效。 方法 在一项平行组、多中心、随机、对照3期试验中，我们比较了吉西他滨联合顺铂诱导化疗加同步放化疗与单独采用同步放化疗的疗效。本试验以1:1的比例将局部区域晚期鼻咽癌患者随机分组，分别接受吉西他滨（剂量为每平方米体表面积1 g，在第1天和第8天给药）联合顺铂（剂量为每平方米体表面积80 mg，在第1天给药）（上述两种药物均每3周给药一次，给药3个周期）加放化疗（同步应用顺铂[剂量为每平方米体表面积100 mg，每3周给药一次，给药3个周期]加调强放疗）或单独接受放化疗。主要终点是意向治疗人群的无复发生存率（即无疾病复发[远处转移或局部区域复发]且无任何原因死亡）。次要终点包括总生存率、治疗依从性和安全性。 结果 共有480例患者被纳入试验（诱导化疗组242例患者，标准治疗组238例患者）。在中位随访42.7个月时，诱导化疗组和标准治疗组的3年无复发生存率分别为85.3%和76.5%（复发或死亡的分层风险比，0.51；95%置信区间[CI]，0.34~0.77；P=0.001）。3年总生存率分别为94.6%和90.3%（死亡的分层风险比，0.43；95% CI，0.24~0.77）。共有96.7%的患者完成了3个周期的诱导化疗。诱导化疗组和标准治疗组的3或4级急性不良事件发生率分别为75.7%和55.7%，诱导化疗组的中性粒细胞减少、血小板减少、贫血、恶心和呕吐发生率高于标准治疗组。诱导化疗组和标准治疗组的3或4级迟发性毒性作用发生率分别为9.2%和11.4%。 结论 在局部区域晚期鼻咽癌患者中，与单独采用放化疗相比，在放化疗的基础上加用诱导化疗显著提高了患者的无复发生存率和总生存率。（由中国教育部创新团队发展计划等资助；在ClinicalTrials.gov注册号为NCT01872962。） Yuan Zhang, Lei Chen, Guo-Qing Hu, et al. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. DOI: 10.1056/NEJMoa1905287 apalutamide治疗转移性去势敏感性前列腺癌 Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer 摘 要 背景 apalutamide是雄激素受体的配体结合域抑制剂。目前尚未明确在转移性去势敏感性前列腺癌患者中，与雄激素剥夺治疗（ADT）加用安慰剂相比，ADT加用apalutamide可否延长患者的影像学无进展生存期和总生存期。 方法 在这项双盲、3期试验中，我们将转移性去势敏感性前列腺癌患者随机分组，分别在ADT的基础上加用apalutamide（每日240 mg）或安慰剂。本试验允许患者接受过针对局部疾病的治疗和多西他赛治疗。主要终点是影像学无进展生存期和总生存期。 结果 共有525例患者被分配接受apalutamide+ADT治疗，527例患者被分配接受安慰剂+ADT治疗。患者中位年龄为68岁。共有16.4%的患者接受过前列腺切除术或局部疾病放疗，10.7%接受过多西他赛治疗；62.7%患高容量疾病，37.3%患低容量疾病。在中位随访时间为22.7个月的第一次期中分析时，apalutamide组和安慰剂组的24个月影像学无进展生存率分别为68.2%和47.5%（影像学进展或死亡的风险比，0.48；95%置信区间[CI]，0.39~0.60；P<0.001）。apalutamide组的24个月总生存率也高于安慰剂组（apalutamide组82.4% vs.安慰剂组73.5%；死亡的风险比，0.67；95% CI，0.51~0.89；P=0.005）。apalutamide组和安慰剂组的3或4级不良事件发生率分别为42.2%和40.8%，apalutamide组的皮疹发生率高于安慰剂组。 结论 在这项纳入转移性去势敏感性前列腺癌患者的试验中，ADT+apalutamide组的总生存期和影像学无进展生存期均显著超过ADT+安慰剂组，且两组的副作用无显著差异。（由Janssen Research and Development资助；TITAN在ClinicalTrials.gov注册号为NCT02489318。） Kim N. Chi, Neeraj Agarwal, Anders Bjartell, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. DOI: 10.1056/NEJMoa1903307 Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma 鼻咽癌的吉西他滨联合顺铂诱导化疗 Abstract Background Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. Methods In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. Results A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P=0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. Conclusion Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.) Yuan Zhang, Lei Chen, Guo-Qing Hu, et al. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. DOI: 10.1056/NEJMoa1905287 Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer apalutamide治疗转移性去势敏感性前列腺癌 Abstract Background Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression–free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. Methods In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression–free survival and overall survival. Results A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. Conclusion In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression–free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.) Kim N. Chi, Neeraj Agarwal, Anders Bjartell, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. DOI: 10.1056/NEJMoa1903307 版权信息 |
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来自： 生物_医药_科研 > 《2019ASCO》
