Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303
Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303
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DOI：
10.1200/jco.18.01994
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发表时间：
2019-07-20
影响因子：
45.3
通讯作者：
Leonard, John P.
中科院分区：
文献类型：
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作者：
Bartlett, Nancy L.;Wilson, Wyndham H.;Leonard, John P.
CALLISAlliance/CALGB 50303（NCT 00118209）是一项组间、III期研究，比较了剂量调整的依托泊苷、泼尼松、长春新碱、环磷酰胺、多柔比星和利妥昔单抗（DA-EPOCH-R）与标准利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）作为弥漫性大B细胞淋巴瘤的一线治疗。主要目标是无进展生存期（PFS）;次要临床目标包括反应率、总生存期（OS）和安全性。在2005年至2013年期间，登记了524例患者; 491例符合条件的患者被纳入最终分析。大多数患者（74%）患有III期或IV期疾病;国际预后指数（IPI）风险组包括26% IPI 0 - 1，37% IPI 2，25% IPI 3和12% IPI 4 - 5。在中位随访5年时，两组之间的PFS无统计学差异（风险比，0.93; 95% CI，0.68 ~ 1.27; P = .65），DA-EPOCH-R的2年PFS率为78.9%（95% CI，73.8%至84.2%），R-CHOP为75.5%（95% CI，70.2%至81.1%）。OS无差异（风险比，1.09; 95% CI，0.75 - 1.59; P = 0.64），DA-EPOCH-R和R-CHOP的2年OS率分别为86.5%（95% CI，82.3%-91%）和85.7%（95% CI，81.4%-90.2%）。DA-EPOCH-R组3级和4级不良事件比R-CHOP组更常见（P <0.001），包括感染（分别为16.9%和10.7%）、发热性中性粒细胞减少（分别为35.0%和17.7%）、粘膜炎（分别为8.4%和2.1%）和神经病变（分别为18.6%和3.3%）。5例治疗相关死亡（2.1%）发生在每个arm. CONCLUSION在50303研究人群中，更密集，输注DA-EPOCH-R毒性更大，并没有改善PFS或OS相比，R-CHOP。与历史对照相比，R-CHOP的结果更有利，这表明潜在的患者选择偏倚，并可能排除结果对特定风险亚组的普遍性。
PURPOSEAlliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.PATIENTS AND METHODSPatients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.RESULTSBetween 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.CONCLUSIONIn the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.