Fornecker Luc-Matthieu, Lazarovici Julien, Aurer Igor, Casasnovas René-Olivier, Gac Anne-Claire, Bonnet Christophe, Bouabdallah Krimo, Feugier Pierre, Specht Lena, Molina Lysiane, Touati Mohamed, Borel Cécile, Stamatoullas Aspasia, Nicolas-Virelizier Emmanuelle, Pascal Laurent, Lugtenburg Pieternella, Di Renzo Nicola, Vander Borght Thierry, Traverse-Glehen Alexandra, Dartigues Peggy, Hutchings Martin, Versari Annibale, Meignan Michel, Federico Massimo, André Marc
Institut de Cancérologie Strasbourg Europe (ICANS) and University of Strasbourg, Strasbourg, France.
Gustave Roussy, Villejuif, France.
J Clin Oncol. 2023 Jan 10;41(2):327-335. doi: 10.1200/JCO.21.01281. Epub 2022 Jul 22.
The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979).
BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD.
Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively.
BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.
早期预后不良的霍奇金淋巴瘤患者的预后仍不尽人意。我们评估了本妥昔单抗联合多柔比星、长春花碱和达卡巴嗪（BV-AVD）用于先前未经治疗的早期预后不良霍奇金淋巴瘤的疗效和安全性（ClinicalTrials.gov标识符：NCT02292979）。
BREACH是一项多中心、随机、开放标签的II期试验。符合条件的患者年龄在18至60岁之间，且至少有一项不良的欧洲癌症研究与治疗组织/淋巴瘤研究组织（EORTC/LYSA）标准。患者被随机分配（2:1）接受四个周期的BV-AVD或标准的多柔比星、博来霉素、长春新碱和达卡巴嗪（ABVD）方案，随后进行30 Gy的受累淋巴结放疗。主要终点是由专家独立审查使用迪耶普评分法评估两个周期后的正电子发射断层扫描（PET）缓解率。该研究旨在检验BV-AVD两个周期后的PET阴性率是否优于75%。我们假设BV-AVD两个周期后的PET阴性率会提高至10%。
2015年3月至2016年10月期间，共纳入170例患者。两个周期后，达到了研究的主要终点：BV-AVD组113例患者中有93例（82.3%；90%CI，75.3%至88.0%）PET阴性（迪耶普评分1 - 3），而ABVD组57例患者中有43例（75.4%；90%CI，64.3%至84.5%）。BV-AVD组和ABVD组的2年无进展生存期（PFS）分别为97.3%（95%CI，91.9%至99.1%）和92.6%（95%CI，81.4%至97.2%）。高代谢肿瘤总体积与显著更短的PFS相关（风险比，17.9；95%CI，2.2至145.5；P <.001）。对于高代谢肿瘤总体积的患者，BV-AVD组和ABVD组的2年PFS率分别为90.9%（95%CI，74.4%至97.0%）和70.7%（95%CI，39.4%至87.9%）。
与ABVD相比，BV-AVD在两个周期后PET阴性率有所改善。
