Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Int J Cancer. 2019 Aug 1;145(3):857-868. doi: 10.1002/ijc.32163. Epub 2019 Mar 4.
We analyzed the predictive potential of pretreatment soluble carbonic anhydrase IX levels (sCAIX) for the efficacy of bevacizumab in the phase III neoadjuvant GeparQuinto trial. sCAIX was determined by enzyme-linked immunosorbent assay (ELISA). Correlations between sCAIX and pathological complete response (pCR), disease-free and overall survival (DFS, OS) were assessed with logistic and Cox proportional hazard regression models using bootstrapping for robust estimates and internal validation. 1,160 HER2-negative patient sera were analyzed, of whom 577 received bevacizumab. Patients with low pretreatment sCAIX had decreased pCR rates (12.1 vs. 20.1%, p = 0.012) and poorer DFS (adjusted 5-year DFS 71.4 vs. 80.5 months, p = 0.010) compared to patients with high sCAIX when treated with neoadjuvant chemotherapy (NCT). For patients with low sCAIX, pCR rates significantly improved upon addition of bevacizumab to NCT (12.1 vs. 20.4%; p = 0.017), which was not the case in patients with high sCAIX (20.1% for NCT vs. 17.0% for NCT-B, p = 0.913). When analyzing DFS we found that bevacizumab improved 5-year DFS for patients with low sCAIX numerically but not significantly (71.4 vs. 78.5 months; log rank 0.234). In contrast, addition of bevacizumab worsened 5-year DFS for patients with high sCAIX (81 vs. 73.6 months, log-rank 0.025). By assessing sCAIX levels we identified a patient cohort in breast cancer that is potentially undertreated with NCT alone. Bevacizumab improved pCR rates in this group, suggesting sCAIX is a predictive biomarker for bevacizumab with regards to treatment response. Our data also show that bevacizumab is not beneficial in patients with high sCAIX.
我们分析了预处理可溶性碳酸酐酶 IX 水平（sCAIX）对 III 期新辅助 GeparQuinto 试验贝伐珠单抗疗效的预测潜力。sCAIX 通过酶联免疫吸附测定（ELISA）测定。使用逻辑和 Cox 比例风险回归模型评估 sCAIX 与病理完全缓解（pCR）、无病生存和总生存（DFS、OS）之间的相关性，并使用引导进行稳健估计和内部验证。分析了 1160 例 HER2 阴性患者的血清，其中 577 例接受了贝伐珠单抗治疗。与高 sCAIX 患者相比，低预处理 sCAIX 患者的 pCR 率较低（12.1%对 20.1%，p=0.012），DFS 较差（调整后的 5 年 DFS 为 71.4 对 80.5 个月，p=0.010），当接受新辅助化疗（NCT）时。对于低 sCAIX 患者，NCT 联合贝伐珠单抗治疗后 pCR 率显著提高（12.1%对 20.4%；p=0.017），而高 sCAIX 患者则不然（NCT 为 20.1%，NCT-B 为 17.0%，p=0.913）。当分析 DFS 时，我们发现贝伐珠单抗改善了低 sCAIX 患者的 5 年 DFS，但没有显著改善（71.4 对 78.5 个月；对数秩 0.234）。相比之下，高 sCAIX 患者添加贝伐珠单抗会降低 5 年 DFS（81 对 73.6 个月，对数秩 0.025）。通过评估 sCAIX 水平，我们在乳腺癌患者中确定了一个潜在的 NCT 治疗不足的患者队列。贝伐珠单抗提高了该组的 pCR 率，表明 sCAIX 是治疗反应方面贝伐珠单抗的预测生物标志物。我们的数据还表明，贝伐珠单抗对高 sCAIX 患者无益。
