Pierre Loap, Delphine Loirat, Marc-Henri Stern, Jean-Yves Pierga, Kim Cao, Anne Vincent -Salomon, Frederique Berger, Alain Fourquet, Youlia Kirova
{"title":"奥拉帕尼联合乳腺放疗治疗TNBC残余病变的安全性和潜在放射增敏效应：RADIOPARP I期试验的长期结果：奥拉帕尼联合TNBC放疗的安全性和放射增敏性","authors":"Pierre Loap, Delphine Loirat, Marc-Henri Stern, Jean-Yves Pierga, Kim Cao, Anne Vincent -Salomon, Frederique Berger, Alain Fourquet, Youlia Kirova","doi":"10.1016/j.ijrobp.2025.05.013","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant therapy face a high risk of locoregional recurrence, particularly when homologous recombination deficiency (HRD) is present. HRD tumors, characterized by impaired double-strand break repair, are theoretically sensitive to PARP inhibitors through synthetic lethality. This phase I trial (XXXXX) evaluated the long-term safety and potential radiosensitizing effects of Olaparib combined with breast radiotherapy in TNBC patients.</p><p><strong>Materials and methods: </strong>This dose-escalation trial enrolled 24 non-metastatic TNBC patients treated between 2015 and 2019. Patients had either residual disease after neoadjuvant therapy (n=21, adjuvant setting) or unresectable tumors (n=3, preoperative setting). Olaparib was administered at escalating doses (50-200 mg BID) for seven days before normofractionated radiotherapy (50-50.4 Gy in 25-28 fractions). HRD status was determined using genomic analyses. Safety was assessed through dose-limiting toxicities (DLTs) and long-term adverse events, while secondary endpoints included locoregional recurrence-free survival (LRRFS), metastasis-free survival (MFS), and overall survival (OS).</p><p><strong>Results: </strong>Median follow-up was 59 months. No grade ≥3 toxicities were reported, and grade 2 toxicities (fibrosis and telangiectasias) were rare. Among HRD patients (n=13), no locoregional recurrences were observed, while three of eight homologous recombination proficient (HRP) patients experienced recurrences (p=0.024). Five-year LRRFS was 100% for HRD patients and 60.0% for HRP patients. MFS was 69.8%, and OS was 73.5%, with no significant differences by HRD status.</p><p><strong>Conclusion: </strong>The XXXXX trial demonstrates the long-term safety of combining Olaparib with radiotherapy and suggests its potential to enhance locoregional control in HRD tumors. Further studies are warranted to confirm these findings and refine treatment strategies for high-risk TNBC patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: XXXXXXX.</p>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":" ","pages":""},"PeriodicalIF":6.4000,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and potential radiosensitizing effect of Olaparib in combination with breast radiotherapy for TNBC patients with residual disease: long-term results from the RADIOPARP Phase I Trial: Safety and Radiosensitization of Olaparib with Radiotherapy in TNBC.\",\"authors\":\"Pierre Loap, Delphine Loirat, Marc-Henri Stern, Jean-Yves Pierga, Kim Cao, Anne Vincent -Salomon, Frederique Berger, Alain Fourquet, Youlia Kirova\",\"doi\":\"10.1016/j.ijrobp.2025.05.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant therapy face a high risk of locoregional recurrence, particularly when homologous recombination deficiency (HRD) is present. HRD tumors, characterized by impaired double-strand break repair, are theoretically sensitive to PARP inhibitors through synthetic lethality. This phase I trial (XXXXX) evaluated the long-term safety and potential radiosensitizing effects of Olaparib combined with breast radiotherapy in TNBC patients.</p><p><strong>Materials and methods: </strong>This dose-escalation trial enrolled 24 non-metastatic TNBC patients treated between 2015 and 2019. Patients had either residual disease after neoadjuvant therapy (n=21, adjuvant setting) or unresectable tumors (n=3, preoperative setting). Olaparib was administered at escalating doses (50-200 mg BID) for seven days before normofractionated radiotherapy (50-50.4 Gy in 25-28 fractions). HRD status was determined using genomic analyses. Safety was assessed through dose-limiting toxicities (DLTs) and long-term adverse events, while secondary endpoints included locoregional recurrence-free survival (LRRFS), metastasis-free survival (MFS), and overall survival (OS).</p><p><strong>Results: </strong>Median follow-up was 59 months. No grade ≥3 toxicities were reported, and grade 2 toxicities (fibrosis and telangiectasias) were rare. Among HRD patients (n=13), no locoregional recurrences were observed, while three of eight homologous recombination proficient (HRP) patients experienced recurrences (p=0.024). Five-year LRRFS was 100% for HRD patients and 60.0% for HRP patients. MFS was 69.8%, and OS was 73.5%, with no significant differences by HRD status.</p><p><strong>Conclusion: </strong>The XXXXX trial demonstrates the long-term safety of combining Olaparib with radiotherapy and suggests its potential to enhance locoregional control in HRD tumors. Further studies are warranted to confirm these findings and refine treatment strategies for high-risk TNBC patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: XXXXXXX.</p>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-05-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Oncology Biology Physics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijrobp.2025.05.013\",\"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":"International Journal of Radiation Oncology Biology Physics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijrobp.2025.05.013","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Safety and potential radiosensitizing effect of Olaparib in combination with breast radiotherapy for TNBC patients with residual disease: long-term results from the RADIOPARP Phase I Trial: Safety and Radiosensitization of Olaparib with Radiotherapy in TNBC.
Introduction: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant therapy face a high risk of locoregional recurrence, particularly when homologous recombination deficiency (HRD) is present. HRD tumors, characterized by impaired double-strand break repair, are theoretically sensitive to PARP inhibitors through synthetic lethality. This phase I trial (XXXXX) evaluated the long-term safety and potential radiosensitizing effects of Olaparib combined with breast radiotherapy in TNBC patients.
Materials and methods: This dose-escalation trial enrolled 24 non-metastatic TNBC patients treated between 2015 and 2019. Patients had either residual disease after neoadjuvant therapy (n=21, adjuvant setting) or unresectable tumors (n=3, preoperative setting). Olaparib was administered at escalating doses (50-200 mg BID) for seven days before normofractionated radiotherapy (50-50.4 Gy in 25-28 fractions). HRD status was determined using genomic analyses. Safety was assessed through dose-limiting toxicities (DLTs) and long-term adverse events, while secondary endpoints included locoregional recurrence-free survival (LRRFS), metastasis-free survival (MFS), and overall survival (OS).
Results: Median follow-up was 59 months. No grade ≥3 toxicities were reported, and grade 2 toxicities (fibrosis and telangiectasias) were rare. Among HRD patients (n=13), no locoregional recurrences were observed, while three of eight homologous recombination proficient (HRP) patients experienced recurrences (p=0.024). Five-year LRRFS was 100% for HRD patients and 60.0% for HRP patients. MFS was 69.8%, and OS was 73.5%, with no significant differences by HRD status.
Conclusion: The XXXXX trial demonstrates the long-term safety of combining Olaparib with radiotherapy and suggests its potential to enhance locoregional control in HRD tumors. Further studies are warranted to confirm these findings and refine treatment strategies for high-risk TNBC patients.
期刊介绍：
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.
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