银耳霉素
杜瓦卢马布
医学
癌症
肿瘤科
CD8型
淋巴细胞
内科学
免疫疗法
免疫系统
免疫学
无容量
易普利姆玛
作者
Renata Ferrarotto,Diana Bell,Maria Laura Rubin,Katherine A. Hutcheson,Jason M. Johnson,Ryan P. Goepfert,Jack Phan,Yasir Y. Elamin,Danice Torman,Carla L. Warneke,Amy C. Hessel,Adam S. Garden,Jeffrey N. Myers,Faye M. Johnson,J. Jack Lee,Andrew G. Sikora,Maura L. Gillison,Bonnie S. Glisson,Neil D. Gross
标识
DOI:10.1158/1078-0432.ccr-19-3977
摘要
In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC.Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes.Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence.Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.
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