Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Disease: Primary Aggregated Analysis of All Baskets from the Phase II Randomized EXTEND Trial.

Methods

EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomly assigned to MDT + SOC versus SOC in one of the six baskets (breast, pancreas, kidney, two prostate baskets, and an other basket) with basket-specific stratification and powering.

EXTEND是一项多中心随机II期试验。随机分配了1-5个转移灶的患者到MDT + SOC组与SOC组，分别在六个特定疾病组（乳腺、胰腺、肾脏、两个前列腺组和其他组）进行，每个疾病组都有特定的分层和功效。

PFS, the primary end point, was prespecified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets.

无进展生存期（PFS），主要终点，在每个疾病组的按方案集、所有疾病组以及排除前列腺疾病组的所有疾病组中预先设定。

Exploratory end points included circulating tumor DNA (ctDNA) and immune profiling.

探索性终点包括循环肿瘤DNA（ctDNA）和免疫表型。

Results

From 2018 through 2023, 521 patients were screened, 350 were randomly assigned, and 334 were analyzed per protocol (MDT + SOC, n = 166; SOC, n = 168).

从2018年到2023年，共筛查了521名患者，350名被随机分配，按照方案分析了334名患者（MDT + SOC，n = 166；SOC，n = 168）。

Radiotherapy was used as MDT for 98% of metastases (370/379).

放射治疗作为MDT用于98%的转移灶（370/379）。

Overall, after a median follow-up of 53 months, PFS was improved with MDT + SOC (hazard ratio[HR], 0.54 [95% CI, 0.41 to 0.72], P < .001).

总体而言，经过中位随访53个月后，MDT + SOC组的PFS得到了改善（风险比[HR]，0.54 [95% CI, 0.41至0.72]，P < .001）。

Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60 [95% CI, 0.40 to 0.89]).

同样，排除前列腺疾病组后，PFS也得到了改善（HR，0.60 [95% CI, 0.40至0.89]）。

Within each basket, PFS superiority was identified for the pancreas, prostate, and other baskets, whereas the breast and kidney baskets were inconclusive.

在每个治疗组中，胰腺、前列腺和其他治疗组显示出无进展生存期（PFS）的优势，而乳腺和肾脏治疗组的结果尚不明确。

At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3 months postenrollment correlated with improved survival. MDT + SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority.

在入组时，可检测到的循环肿瘤DNA（ctDNA）与较短的无进展生存期（PFS）和生存期相关；相反，在入组后3个月清除ctDNA与改善的生存期相关。MDT+SOC诱导的全身免疫激活在显示出PFS优势的治疗组中最为明显。

Conclusions

The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease.

第二阶段EXTEND试验支持将MDT加入SOC用于寡转移性疾病。

Histology-specific efficacy signals were identified for phase III testing.

为第三阶段测试识别了组织学特异性的疗效信号。

Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA and point to systemic immune responses as a possible mechanism of benefit from MDT.

转化研究的见解表明，使用ctDNA优化寡转移状态的定义具有潜力，并指出全身免疫反应可能是MDT受益的可能机制。