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Abstract：
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients.
METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1.
RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0.
CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC.
CONCLUSIONS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.
METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1.
RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0.
CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC.
CONCLUSIONS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.
摘要：
背景：肝内胆管癌（ICC）的特征是预后不佳，治疗选择有限。探讨磷酸酶和张力同源物(PTEN)作为ICC蛋白酶体抑制的生物标志物,我们进行了一项II期试验,以评估硼替佐米在PTEN缺乏的晚期ICC患者中的二线疗效.
方法：在2017年7月1日至2021年12月31日期间，通过PTEN免疫组织化学染色筛选了我们中心的130例晚期ICC患者，最终纳入16例患者，并在21天周期的第1、4、8和11天用1.3mg/m2的单药硼替佐米治疗。主要终点是根据实体瘤v1.1的反应评估标准的客观反应率（ORR）。
结果：中位随访时间为6.55个月（95％置信区间[CI]：0.7-19.9个月）。在16名患者中，ORR为18.75%(3/16),疾病控制率为43.75%(7/16)。意向治疗患者的中位无进展生存期为2.95个月（95%CI：2.1-5.1个月），中位总生存期（mOS）为7.2个月（95%CI：0.7-21.6个月）。16例患者报告了任何级别的治疗相关不良事件，血栓减少是最常见的毒性。PTEN染色评分为0的患者比染色评分>0的患者更有可能从硼替佐米中获益。
结论：硼替佐米作为PTEN缺陷ICC患者的二线药物，产生了令人鼓舞的客观反应和良好的OS。我们的发现表明硼替佐米是PTEN缺陷ICC患者的有希望的治疗选择。
结论：肝内胆管癌（ICC）二线选择的策略有限。这项研究者发起的2期研究评估了硼替佐米在具有磷酸酶和张力同源性缺乏的ICC患者中的应用。在意向治疗队列中，总有效率为18.75%，总生存期为7.2个月。这些结果证明了在患有PTEN缺乏症的ICC患者中进一步开发硼替佐米。
方法：在2017年7月1日至2021年12月31日期间，通过PTEN免疫组织化学染色筛选了我们中心的130例晚期ICC患者，最终纳入16例患者，并在21天周期的第1、4、8和11天用1.3mg/m2的单药硼替佐米治疗。主要终点是根据实体瘤v1.1的反应评估标准的客观反应率（ORR）。
结果：中位随访时间为6.55个月（95％置信区间[CI]：0.7-19.9个月）。在16名患者中，ORR为18.75%(3/16),疾病控制率为43.75%(7/16)。意向治疗患者的中位无进展生存期为2.95个月（95%CI：2.1-5.1个月），中位总生存期（mOS）为7.2个月（95%CI：0.7-21.6个月）。16例患者报告了任何级别的治疗相关不良事件，血栓减少是最常见的毒性。PTEN染色评分为0的患者比染色评分>0的患者更有可能从硼替佐米中获益。
结论：硼替佐米作为PTEN缺陷ICC患者的二线药物，产生了令人鼓舞的客观反应和良好的OS。我们的发现表明硼替佐米是PTEN缺陷ICC患者的有希望的治疗选择。
结论：肝内胆管癌（ICC）二线选择的策略有限。这项研究者发起的2期研究评估了硼替佐米在具有磷酸酶和张力同源性缺乏的ICC患者中的应用。在意向治疗队列中，总有效率为18.75%，总生存期为7.2个月。这些结果证明了在患有PTEN缺乏症的ICC患者中进一步开发硼替佐米。
