PEARL：人类表皮生长因子受体 2 阴性乳腺癌新辅助化疗前在 Pembrolizumab 基础上增加放疗的 Ib/II 期生物标志物研究。

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2024-09-19 DOI:10.1200/jco.24.00003

Alice Y Ho,Stephen Shiao,Samantha A Kobald,Jonathan Chen,Dan G Duda,Amy Ly,Veerle Bossuyt,Hae Lin Cho,Brittany Arnold,Simon Knott,Gaorav P Gupta,Philomena McAndrew,Scott Karlan,Mourad Tighiouart,Alona Muzikansky,Reva Basho,Heather McArthur

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Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti-PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS).\r\n\r\nRESULTS\r\nSixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2-) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2-, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2- had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, -41.88 to -6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, -41.88 to -6.30; P = .009), compared with baseline. 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引用次数: 0

摘要

材料与方法在三阴性乳腺癌（TNBC）和激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）乳腺癌患者中开展了 pembrolizumab 联合 RT 的 I/IIb 期试验。所有患者都接受了pembrolizumab治疗，然后进行了第二周期+RT（抗PD1/RT）治疗，24 Gy/每天三次，每次分次作用于乳腺肿瘤，然后接受新辅助化疗（NAC）。分别在基线、抗PD1治疗后和抗PD-RT治疗后采集血液和肿瘤活检组织。主要终点是安全性和肿瘤浸润淋巴细胞（TILs）的变化。次要终点是病理完全反应（pCR）、残留癌负担（RCB）率和无事件生存期（EFS）。结果有66例I-III期乳腺癌患者（54例TNBC，12例HR+/HER2-）入组。中位随访时间为 32 个月。达到安全终点。毒性≥3级的发生率为41%。TNBC、HR+/HER2-和整个队列的pCR率分别为59.2%、33.3%和54.5%。共有77.8%的TNBC患者和41.6%的HR+/HER2-患者接近pCR（RCB 0-1）。3年生存率为80%。在整个队列中，与基线相比，抗PD1（中位数综合阳性评分[CPS]，7.49-23.20；95% CI，-41.88-6.30；P = .044）和抗PD1/RT（中位数CPS，7.49-23.41；95% CI，-41.88-6.30；P = .009）后PD-L1表达增加。在 TNBC 中，在抗 PD1 的基础上加用 RT 可显著降低 TILs（28.9%-17.1%；95% CI，2.46-21.09；P = .014）。结论尽管在NAC期间没有使用pembrolizumab，但使用pembrolizumab进行术前RT是安全的，并能获得较高的pCR率和3年EFS。PD-L1和TILs可能是术前抗PD1/RT反应的预测性生物标志物。在抗PD1基础上加用RT后TILs的减少凸显了治疗排序的重要性。

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PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PURPOSE To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer. MATERIALS AND METHODS A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti-PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS). RESULTS Sixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2-) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2-, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2- had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, -41.88 to -6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, -41.88 to -6.30; P = .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09; P = .014). Baseline TILs correlated with PD-L1 expression and TNF-a. CONCLUSION Preoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.