Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with , , and is complete. From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0–4·5) for patients in the standard-of-care group versus 7·2 months (4·5–10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35–0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2–not reached] 2·2 months [95% CI 2·0–4·5]; HR 0·41, 95% CI 0·22–0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5–8·7] 4·2 months [1·8–5·5]; 0·78, 0·43–1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. National Cancer Institute.

中文翻译：

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对寡进行性乳腺癌或非小细胞肺癌患者进行标准护理全身治疗，联合或不联合立体定向全身放射治疗（综合使用放疗来阻断 [CURB] 寡进行性）：开放标签、随机、对照、阶段2 学习

大多数转移性癌症患者最终会对全身治疗产生耐药性，其中一些患者的疾病进展有限（即寡进展）。我们的目的是评估针对寡进展部位的立体定向全身放射治疗 (SBRT) 是否可以改善患者的治疗效果。我们在至少接受过一线全身治疗后的寡进展性转移性乳腺癌或非小细胞肺癌 (NSCLC) 患者中进行了 SBRT 2 期、开放标签、随机对照试验，寡进展定义为 5 或PET-CT 或 CT 上的进展性病变较少。年龄 18 岁或以上的患者从美国纽约州的一个三级癌症中心以及纽约州和新泽西州的六个附属区域中心入组，在标准护理（标准治疗）之间进行 1:1 随机分组。 -护理组）和 SBRT 加标准护理（SBRT 组）。随机化是通过基于计算机的算法进行的，根据转移进展部位的数量、受体或驱动基因改变状态、原发部位和先前接受的全身治疗类型进行分层。患者和研究人员并未被掩盖治疗分配情况。主要终点是长达 12 个月的无进展生存期。我们按疾病部位对主要终点进行了预先指定的亚组分析。所有分析均在意向治疗人群中进行。该研究已在 、 、 注册，并且已完成。从2019年1月1日到2021年7月31日，106名患者被随机分配至标准护理组（n=51；23名乳腺癌患者和28名非小细胞肺癌患者）或SBRT加标准护理组（n=55；24名患者）乳腺癌患者和 31 名非小细胞肺癌 (NSCLC) 患者）。47 名乳腺癌患者中有 16 名 (34%) 患有三阴性疾病，59 名 NSCLC 患者中有 51 名 (86%) 没有可操作的驱动突变。在预先计划的中期分析中达到主要疗效终点后，该研究在达到目标样本量之前就结束了累积。标准护理组患者的中位随访时间为 11·6 个月，SBRT 组患者的中位随访时间为 12·1 个月。标准治疗组患者的中位无进展生存期为 3·2 个月 (95% CI 2·0–4·5)，而标准治疗组患者的中位无进展生存期为 7·2 个月 (4·5–10·0)。 SBRT 组（风险比 [HR] 0·53，95% CI 0·35–0·81；p=0·0035）。SBRT 组 NSCLC 患者的中位无进展生存期高于标准治疗组 NSCLC 患者（10·0 个月 [7·2 - 未达到] 2·2 个月 [95% CI 2·0–4·5]；HR 0·41，95% CI 0·22–0·75；p=0·0039），但乳腺癌患者没有发现差异（4·4 个月[2· 5–8·7] 4·2 个月 [1·8–5·5]；0·78，0·43–1·43；p=0·43）。标准护理组中有 21 名患者 (41%) 发生了 2 级或更严重的不良事件，SBRT 组有 34 名患者 (62%) 发生了 2 级或更严重的不良事件。SBRT 组中有 9 名 (16%) 患者出现 2 级或更严重的 SBRT 相关毒性，包括胃肠道反流病、疼痛加剧、放射性肺炎、臂丛神经病和低血细胞计数。该试验表明，与仅标准护理组相比，SBRT 加标准护理组的无进展生存期有所增加。转移性 NSCLC 患者的少进展可以通过 SBRT 加标准护理得到有效治疗，与仅标准护理相比，无进展生存期增加四倍以上。相比之下，少进展型乳腺癌患者没有观察到任何益处。有必要进行进一步的研究来验证这些发现并了解不同的好处。国家癌症研究所。