Song Yuqin, Zhou Keshu, Zou Dehui, Li Dengju, Hu Jianda, Yang Haiyan, Zhang Huilai, Ji Jie, Xu Wei, Jin Jie, Lv Fangfang, Feng Ru, Gao Sujun, Zhou Daobin, Tam Constantine S, Simpson David, Wang Michael, Phillips Tycel J, Opat Stephen, Fang Cheng, Sun Shaohui, Zhu Jun
Peking University Cancer Hospital and Institute, Beijing, China.
Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Cancer Med. 2023 Sep;12(18):18643-18653. doi: 10.1002/cam4.6473. Epub 2023 Sep 14.
We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second-line versus later-line. Here, we present an updated pooled analysis with a longer follow-up of 35.2 months.
Data were pooled from two studies-BGB-3111-AU-003 (NCT02343120) and BGB-3111-206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second-line and the later-line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety.
Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second-line and 71 (63.4%) patients as later-line therapy. After weighting, OS was significantly improved in the second-line versus later-line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second-line versus later-line group (27.8 vs. 22.1 months). ORR was numerically higher in the second-line versus later-line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups.
Zanubrutinib in second-line treatment was associated with significantly improved OS compared with later-line treatment of R/R MCL.
我们之前报告了两项泽布替尼治疗复发或难治性（R/R）套细胞淋巴瘤（MCL）研究的汇总分析结果，显示泽布替尼用于二线治疗对比后续线治疗时生存结果更佳。在此，我们呈现一项随访时间更长（35.2个月）的更新汇总分析。
数据来自泽布替尼治疗R/R MCL的两项研究——BGB-3111-AU-003（NCT02343120）和BGB-3111-206（NCT03206970）。根据泽布替尼的治疗线将患者分为两组：二线组和后续线组。采用逆倾向评分加权法平衡两组间的基线协变量。主要结局为总生存期（OS）。次要结局包括无进展生存期（PFS）、PFS率和OS率、客观缓解率（ORR）、缓解持续时间（DOR）以及安全性。
在112例汇总患者中，41例（36.6%）患者接受泽布替尼作为二线治疗，71例（63.4%）患者接受后续线治疗。加权后，二线组对比后续线组的OS显著改善（HR，0.459[95%CI：0.215，0.98]；p = 0.044），两组的中位OS均不可估计。两组间的PFS相似（HR，0.78[95%CI：0.443，1.373]；p = 0.389），但二线组的中位PFS在数值上长于后续线组（27.8个月对22.1个月）。二线组的ORR在数值上高于后续线组（88.6%对85.7%），两组间的DOR相似（25.2个月对25.1个月）。泽布替尼在两组中的安全性特征相似。
与R/R MCL的后续线治疗相比，泽布替尼二线治疗可显著改善OS。
