{"title":"Pembrolizumab (Pembro) + 同期化放疗 (CCRT) 治疗高风险局部晚期宫颈癌 (LACC) 的 3 期研究:安全性研究结果","authors":"","doi":"10.1016/j.ijrobp.2024.07.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; <em>P</em> = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data.</div></div><div><h3>Materials/Methods</h3><div>Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m<sup>2</sup> QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts.</div></div><div><h3>Results</h3><div>Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the <strong>Table</strong>). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were < 10.0 events per 100 person-months of exposure during any period.</div></div><div><h3>Conclusion</h3><div>Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Phase 3 Study of Pembrolizumab (Pembro) + Concurrent Chemoradiotherapy (CCRT) for High-Risk Locally Advanced Cervical Cancer (LACC): Safety Findings\",\"authors\":\"\",\"doi\":\"10.1016/j.ijrobp.2024.07.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose/Objective(s)</h3><div>In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; <em>P</em> = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data.</div></div><div><h3>Materials/Methods</h3><div>Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m<sup>2</sup> QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts.</div></div><div><h3>Results</h3><div>Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the <strong>Table</strong>). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were < 10.0 events per 100 person-months of exposure during any period.</div></div><div><h3>Conclusion</h3><div>Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase.</div></div>\",\"PeriodicalId\":14215,\"journal\":{\"name\":\"International Journal of Radiation Oncology Biology Physics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2024-10-01\",\"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://www.sciencedirect.com/science/article/pii/S0360301624007661\",\"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://www.sciencedirect.com/science/article/pii/S0360301624007661","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
A Phase 3 Study of Pembrolizumab (Pembro) + Concurrent Chemoradiotherapy (CCRT) for High-Risk Locally Advanced Cervical Cancer (LACC): Safety Findings
Purpose/Objective(s)
In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; P = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data.
Materials/Methods
Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts.
Results
Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the Table). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were < 10.0 events per 100 person-months of exposure during any period.
Conclusion
Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase.
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.