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美国食品药品管理局汇总分析临床研究乳腺癌仅骨转移结局与放射影像学评定

2018年03月12日

来源：SIBCS

虽然骨转移常见于乳腺癌，但是乳腺癌仅骨转移患者的结局和比例尚不明确。

2018年3月9日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国食品药品管理局药品评审研究中心的研究报告，汇总分析了所有临床研究的乳腺癌仅骨转移患者不同结局，并且探讨了研究者与盲法独立集中复核者之间是否存在放射影像学读片的差异。

该研究汇总并且分析了2005年以来转移性乳腺癌治疗新药或生物制剂初始或补充许可证申报共计13项前瞻研究1万521例患者的数据，分三个亚组进行评价：仅骨转移、骨转移合并其他转移、无骨转移。分别对3733例早期患者和2813例晚期患者的盲法独立集中复核，计算早期不一致率和晚期不一致率。

结果发现，所有骨转移患者占49%（范围：42%～73%），仅骨转移患者占12.5%（范围：4%～26%）。

汇总研究者评定的无进展生存和总体生存表明，仅骨转移亚组与其他亚组相比，结局较好：

仅骨转移与合并转移相比，进展风险低36%（风险比：0.64，95%：0.59～0.70）
仅骨转移与无骨转移相比，进展风险低30%（风险比：0.70，95%：0.65～0.76）
仅骨转移与合并转移相比，死亡风险低44%（风险比：0.56，95%：0.50～0.61）
仅骨转移与无骨转移相比，死亡风险低32%（风险比：0.68，95%：0.61～0.76）

仅骨转移亚组与其他亚组相比，早期不一致率较高，晚期不一致率较低。

迄今为止，该回顾为乳腺癌仅骨转移亚组的最大样本分析，表明该亚组自然史可能比较独特。仅骨转移亚组与其他两组相比，当地研究者对进展事件的评定似乎也存在差异。

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

PURPOSE: The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review.

METHODS: We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively.

RESULTS: Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups.

CONCLUSION: To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.