医学
结直肠癌
杜瓦卢马布
临床终点
内科学
肿瘤科
临床研究阶段
放化疗
代理终结点
放射治疗
癌症
免疫疗法
泌尿科
临床试验
无容量
作者
Thomas J. George,Greg Yothers,Samuel A. Jacobs,Gene Grant Finley,James L. Wade,Caio Max Sao Pedro Rocha Lima,Tanios Bekaii‐Saab,Shalu Pahuja,Anuradha Krishnamurthy,John C. Byrd,Melvin Deutsch,Jesus C. Fabregas,James J. Lee,Carmen J. Allegra,Norman Wolmark
标识
DOI:10.1200/jco.2022.40.4_suppl.099
摘要
99 Background: Although immunotherapy shows no benefit in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. Using a “window-of-opportunity” study design, this prospective phase II trial will determine the safety and activity of this approach with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: Stage II/III patients (pts) with MSS rectal cancer undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT) followed by definitive surgery were eligible. Treatment included durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion followed by surgery within 8-12 wks of the final CRT dose. Primary end point (EP): Improvement in modified neoadjuvant rectal cancer (mNAR) score (goal 10.6) compared to historical controls (15.6) targeting a 20% DFS RR reduction and 3-4% absolute OS improvement. Secondary EPs: toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, and exploratory assessments of tumor-infiltrating lymphocytes, tumor Immunoscore, circulating immunologic profiles, and molecular predictors of response. We test H 0 : mNAR ≥15.6 vs H A : mNAR <15.6 at alpha 0.10 one-sided with statistical significance defined as p<0.1. Results: From May 2018 to October 2020, 45 pts were enrolled with 40 pts evaluable for mNAR. Mean mNAR was 12.03 (80% CI: 9.29-14.97) (p=0.06 one-sided). pCR=22.2%; cCR=31.1%; R0 resection=81.0%, and sphincter preservation=71.4%. Side effects were consistent with both CRT and durvalumab safety profile. Most common grade 3 AEs included diarrhea, lymphopenia, and back pain. There was one grade 4 AE (elevated amylase/lipase) and no grade 5 AEs. Remaining secondary and correlative immunologic end points are still being assessed. Conclusions: Durvalumab immediately following CRT prior to surgery for definitive management of rectal cancer was safe and without unexpected short-term toxicities. The primary end point of mean mNAR score was significantly less than our historical control, warranting further investigation. Correlative analyses for immunologic markers of response including PD-(L)1 expression and Immunoscore are ongoing. NCT 03102047. Support: AstraZeneca-Medimmune, NSABP Foundation. Clinical trial information: NCT03102047.
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