下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Immunotherapy-based salvage therapy in advanced soft tissue sarcoma after first-line chemotherapy: a retrospective single-center analysis with emphasis on undifferentiated pleomorphic sarcoma.
基于免疫治疗的方案,尤其是化学免疫治疗,在晚期STS中显示出较传统化疗有PFS获益的提示,其中UPS显示出与疾病控制相关的提示。安全性特征可接受。然而,回顾性设计、历史对照、样本量有限以及总生存数据不成熟等固有局限性,需要谨慎解读。
软组织肉瘤(STS)是一种罕见的间叶组织恶性肿瘤,晚期治疗选择有限。以蒽环类药物为基础的化疗仍是标准治疗方案,但疗效有限且毒性显著,凸显了对更有效策略的需求。
我们回顾性分析了2021年1月至2026年1月期间在天津医科大学肿瘤医院接受PD-1抑制剂为基础治疗的56例晚期STS患者。治疗方案包括单纯免疫治疗或联合化疗或靶向治疗。观察的主要终点为中位无进展生存期(mPFS)和中位总生存期(mOS)。采用Kaplan-Meier法分析生存结局;通过Cox比例风险回归模型确定与预后相关的因素。并将结果与53例仅接受化疗的历史队列患者进行比较。
共纳入56例患者,免疫治疗队列的中位随访时间为19.2个月(范围,1.32-52.8个月)。UPS患者的中位PFS长于非UPS组织学类型患者(P = 0.045)。接受免疫治疗联合化疗的患者中位PFS(P = 0.047)和中位OS(P = 0.046)均长于单纯接受免疫治疗的患者。多因素Cox回归分析确定UPS组织学类型(P = 0.023)和免疫治疗联合化疗(P = 0.047)是与晚期STS中PFS相关的因素。与53例单纯接受化疗的患者相比,以免疫治疗为基础的综合治疗组在总体人群中具有更长的中位PFS(P = 0.023);单纯化疗免疫治疗组(n = 22)也显示出更长的PFS(P = 0.014)。这一关联在UPS亚组中同样被观察到(P = 0.006)。治疗相关不良事件以1-2级为主;未发生4-5级严重不良事件或治疗相关死亡。
INTRODUCTION: Soft tissue sarcomas (STS) are rare mesenchymal malignancies with limited treatment options in advanced stages. Anthracycline-based chemotherapy remains the standard of care but yields modest outcomes with significant toxicity, underscoring the need for more effective strategies. METHODS: We retrospectively analyzed 56 patients with advanced STS who received PD-1 inhibitor-based therapy at Tianjin Medical University Cancer Institute and Hospital between January 2021 and January 2026. Treatment regimens included immunotherapy alone or in combination with chemotherapy or targeted therapy. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival outcomes were analyzed by Kaplan-Meier analysis; factors associated with prognosis were identified by a Cox proportional hazards regression model. Outcomes were compared with a historical cohort of 53 patients treated with chemotherapy alone. RESULTS: A total of 56 patients were included, and the median follow-up time in the immunotherapy cohort was 19.2 months (range, 1.32-52.8 months). Patients with UPS had a longer median PFS than those with non-UPS histology (P = 0.045). Patients receiving immunotherapy combined with chemotherapy had longer median PFS (P = 0.047) and median OS (P = 0.046) compared with those receiving immunotherapy without chemotherapy. Multivariable Cox regression identified UPS histology (P = 0.023) and immunotherapy combined with chemotherapy (P = 0.047) as factors associated with PFS in advanced STS. Compared with 53 patients who received chemotherapy alone, the immunotherapy-based comprehensive treatment group had longer median PFS in the overall population (P = 0.023); the pure chemoimmunotherapy group (n = 22) also showed longer PFS (P = 0.014). This association was also observed in the UPS subgroup (P = 0.006). Treatment-related adverse events were predominantly grade 1-2; no grade 4-5 severe adverse events or treatment-related deaths occurred. DISCUSSION: Immunotherapy-based regimens, particularly chemoimmunotherapy, showed a suggested PFS benefit over conventional chemotherapy in advanced STS, with UPS showing a suggested association with disease control. The safety profile was acceptable. Nevertheless, the limitations inherent to the retrospective design, historical controls, modest sample size, and immature overall survival data warrant cautious interpretation.
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