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
{"title":"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。","authors":"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","doi":"10.1200/jco.24.00003","DOIUrl":null,"url":null,"abstract":"PURPOSE\r\nTo assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.\r\n\r\nMATERIALS AND METHODS\r\nA 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).\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. 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.\r\n\r\nCONCLUSION\r\nPreoperative 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.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1200/jco.24.00003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"PURPOSE\\r\\nTo assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.\\r\\n\\r\\nMATERIALS AND METHODS\\r\\nA 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).\\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. 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.\\r\\n\\r\\nCONCLUSION\\r\\nPreoperative 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.\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/jco.24.00003\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/jco.24.00003","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.