#大药编#NEJM:色瑞替尼联合化疗改善晚期霍奇金淋巴瘤预后

色瑞替尼(Brentuximab vedotin)是CD30抗体,已

被批准用于复发性和难治性霍奇金淋巴瘤。



近期发表在《新英格兰医学杂志》上的临床试验,研究了使用色瑞替尼联合化疗与传统经典的ABVD化疗方案相比的有效性和安全性。


研究方法:

我们进行了多中心、开放的随机对照3期临床研究,纳入了未经治疗的3-4期经典霍奇金淋巴瘤患者。其中664例接受色瑞替尼联合多柔比星、长春新碱和达卡巴嗪(A+AVD)治疗,670例接受多柔比星、博来霉素、长春新碱和达卡巴嗪(ABVD)治疗。

主要研究终点为调整后无进展生存期(到疾病进展、死亡或无完全缓解和更换方案的时间),研究经过独立审查委员会审核。次要终点为总生存期。

研究结果:

在24.6个月的中位随访时间里,2年调整后无进展生存率A+AVD 和ABVD分别为82.1% (95% [CI], 78.8 - 85.0) 和 77.2% (95% CI, 73.7 - 80.4),相差4.9个百分点(HR:0.77; 95% CI, 0.60 - 0.98; P=0.04)。A+AVD组共有28例死亡,ABVD组共有39例死亡(总生存期HR:0.73 [95% CI, 0.45 to 1.18]; P=0.20)。所有次要终点A+AVD方案均有优势。A+AVD组有58%的患者出现中性粒细胞缺乏,ABVD组有45%。A+AVD组出现发热性中性粒细胞缺乏的83名患者中,接受集落刺激因子预防性治疗的患者比不接受预防的比例低(11% vs. 21%)。

A+AVD组发生外周神经病变比例为67%,ABVD组为43%。A+AVD组67%发生外周神经病变的患者在最后随访时得到解决或缓解。A+AVD肺部毒性等于或高于3级的发生率小于1%,而ABVD组为3%。所有在治疗中死亡的患者中,A+AVD组9人中有7人有中性粒细胞减少,ABVD组13人中有11人与肺毒性相关。

研究结论:

在治疗进展性霍奇金淋巴瘤时,A+AVD方案的疗效优于ABVD,2年无进展生存率(包括进展、死亡、未完全缓解或更换治疗方案)高4.9个百分点。


原文:


BACKGROUND

Brentuximab vedotin is an anti-CD30 antibody–drug conjugate that has been approved for relapsed and refractory Hodgkin’s lymphoma.


METHODS

We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin’s lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival.


RESULTS

At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20). All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.


CONCLUSIONS

A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin’s lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. 

 

end

 

Reference: 

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma


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