Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome, Italy; Department of Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy.
Unit of Oncology, University Hospital of Pisa, Pisa, Italy; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
ESMO Open. 2022 Dec;7(6):100606. doi: 10.1016/j.esmoop.2022.100606. Epub 2022 Oct 31.
Colorectal cancer (CRC) is one of the most common cancers; ∼20% of patients have metastases at diagnosis, and 50%-60% subsequently develop metachronous metastases. Bone involvement, despite being rare, is usually associated with higher disease burden, worse prognosis, impaired quality of life, and significant health-related cost. In the last few years, following the positive results of the TRIBE and TRIBE2 trials, the association of FOLFOXIRI plus bevacizumab has become the new standard of care for metastatic CRC. Despite being highly efficacious in all subgroups, little is known about the activity of this regimen in patients with bone metastases.
We carried out a pooled analysis of TRIBE and TRIBE2 studies focusing on patients with skeletal deposits.
Our analyses on the whole population showed that patients with baseline bone involvement reported shorter overall survival [OS; 14.0 versus 26.2 months; hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.46-2.87; P < 0.001] and progression-free survival (PFS; 6.2 versus 11.1 months; HR 1.96, 95% CI 1.42-2.69; P < 0.001) compared with those without bone metastases; no significant interaction with the treatment was reported for PFS (P = 0.094) and OS (P = 0.38). Bone metastases had a negative prognostic implication in the multivariate analysis (HR 2.24, 95% CI 1.54-3.26; P < 0.001). Furthermore, patients with bone lesions at first radiological progression (including those with baseline bone metastases) had a shorter OS compared with those who progressed in other sites (10.4 versus 13.2 months; HR 1.48, 95% CI 1.15-1.91; P = 0.002). A trend toward inferior OS (7.5 versus 11 months, HR 1.50, 95% CI 0.92-2.45; P = 0.10) appeared in patients with basal skeletal deposits compared with those with bone involvement at first radiological progression.
Our study confirmed the negative prognostic impact of bone metastases in CRC. Furthermore, we demonstrated for the first time that the survival advantage of triplet chemotherapy plus bevacizumab is maintained even in this prognostically unfavorable subgroup.
结直肠癌（CRC）是最常见的癌症之一；约 20%的患者在诊断时已有转移，50%-60%随后发生异时性转移。尽管骨转移较为罕见，但通常与更高的疾病负担、更差的预后、生活质量受损和显著的健康相关成本相关。在过去几年中，TRIBE 和 TRIBE2 试验的阳性结果表明，FOLFOXIRI 联合贝伐珠单抗成为转移性 CRC 的新标准治疗方法。尽管在所有亚组中均具有高度疗效，但对于该方案在骨转移患者中的活性知之甚少。
我们对 TRIBE 和 TRIBE2 研究进行了汇总分析，重点关注骨骼沉积物患者。
我们对全人群的分析显示，基线时有骨受累的患者总生存期[OS；14.0 个月与 26.2 个月；风险比（HR）2.04，95%置信区间（CI）1.46-2.87；P<0.001]和无进展生存期（PFS；6.2 个月与 11.1 个月；HR 1.96，95% CI 1.42-2.69；P<0.001）更短；报告的 PFS（P=0.094）和 OS（P=0.38）与治疗无显著相互作用。在多变量分析中，骨转移具有负预后意义（HR 2.24，95% CI 1.54-3.26；P<0.001）。此外，在首次影像学进展时出现骨病变的患者（包括基线时有骨转移的患者）与在其他部位进展的患者相比，OS 更短（10.4 个月与 13.2 个月；HR 1.48，95% CI 1.15-1.91；P=0.002）。与首次影像学进展时出现骨骼沉积的患者相比，首次影像学进展时出现基底骨骼沉积的患者 OS 更差（7.5 个月与 11 个月，HR 1.50，95% CI 0.92-2.45；P=0.10）。
本研究证实了 CRC 骨转移的负预后影响。此外，我们首次证明，三联化疗加贝伐珠单抗的生存优势即使在这种预后不良的亚组中也得以维持。
