A phase II, randomized, open-label study to evaluate low-dose pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy for localized triple-negative breast cancer (TNBC) (PLANeT trial-Pembrolizumab Low dose in Addition to NACT in TNBC).

Trials employing reduced doses of immune checkpoint inhibitors have yielded encouraging activity in several tumor types.

采用降低剂量的免疫检查点抑制剂的试验在几种肿瘤类型中显示出令人鼓舞的活性。

Whether low-dose pembrolizumab enhances pathological complete response when added to NACT in TNBC remains uncertain.

低剂量帕博利珠单抗在三阴性乳腺癌(TNBC)中加入新辅助化疗(NACT)是否能增强病理完全缓解仍不确定。

patients_and_methods

A phase II, open-label, randomized controlled study was conducted at a tertiary cancer center in New Delhi, India.

在印度新德里的一个三级癌症中心进行了一项II期、开放标签、随机对照研究。

Eligible participants had previously untreated stage II-III TNBC and lacked access to standard-dose pembrolizumab.

符合条件的参与者之前未接受过治疗，患有 II-III 期三阴性乳腺癌（TNBC），并且无法获得标准剂量的帕博利珠单抗。

Patients were randomly assigned (1 : 1) to receive dose-dense NACT-four cycles of doxorubicin-cyclophosphamide followed by four cycles of paclitaxel with or without a low dose of pembrolizumab (50 mg every 6 weeks for three cycles).

患者按1:1的比例随机分配接受密集剂量的新辅助化疗（NACT）——四周期多柔比星-环磷酰胺，随后是四周期紫杉醇，患者或接受或不接受低剂量的帕博利珠单抗（每6周50毫克，共三周期）。

The primary endpoint was pathological complete response.

主要终点是病理完全缓解。

Results

Between February 2024 and February 2025, 157 patients were enrolled.

在2024年2月至2025年2月期间，共有157名患者被纳入研究。

Baseline characteristics were comparable between study arms.

研究组之间的基线特征是可比的。

Surgery was completed in 152 patients.

152名患者完成了手术。

In the intention-to-treatpopulation, pathological complete response was achieved in 53.8% [90% confidence interval(CI) 43.9% to 63.5%] of patients receiving low-dose pembrolizumab + NACT versus 40.5% (90% CI 31.1% to 50.4%) with NACT alone, corresponding to an absolute difference of 13.3% (90% CI 0.3% to 26.3%, one-sided P = 0.047).

在意向治疗人群中，接受低剂量帕博利珠单抗加新辅助化疗（NACT）的患者中，53.8%（90%置信区间43.9%至63.5%）实现了病理完全缓解，而仅接受NACT的患者为40.5%（90%置信区间31.1%至50.4%），绝对差异为13.3%（90%置信区间0.3%至26.3%，单侧P = 0.047）。

Among those who underwent surgery, the respective pathological complete response rates were 56.7% and 41.0% (absolute difference 15.7%, one-sided P = 0.031).

在进行手术的患者中，相应的病理完全缓解率分别为56.7%和41.0%（绝对差异15.7%，单侧P = 0.031）。

Grade ≥3 toxicities occurred in 50% of patients in the low-dose pembrolizumab arm and in 59.5% in the control arm.

低剂量派姆单抗组中50%的患者出现了3级或更高级别的毒性反应，对照组则为59.5%。

Conclusions

Addition of low-dose immunotherapy to NACT led to a statistically significant increase in pathological complete response rates, and the benefit appears to be numerically similar to that seen in the KEYNOTE-522 trial. In settings where access to the standard regimen is restricted, a low-dose approach may offer a feasible and cost-effective treatment option for patients with TNBC.

将低剂量免疫治疗添加到新辅助化疗中，病理完全缓解率显著增加，并且在数值上与KEYNOTE-522试验中所见的益处相似。在标准治疗方案难以获取的情况下，低剂量方法可能为三阴性乳腺癌患者提供了一个可行且经济有效的治疗选择。