Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma -the IT-MATTERS study.

IF 2.3 4区 医学 Q3 ONCOLOGY
Pathology & Oncology Research Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI:10.3389/pore.2025.1612084
Eyal Talor, József Tímár, Philip Lavin, John Cipriano, Dusan Markovic, Andrea Ladányi, Andrey Karpenko, Igor Bondarenko, Srboljub Stosic, Hrvoje Sobat, Aliaksandr Zhukavets, Nazim Imamovic, Chih-Yen Chien, Magdalena Bankowska-Wozniak, Mihály Kisely, Rajko Jovic, James Edward Massey Young, Sheng-Po Hao
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引用次数: 0

Abstract

The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naïve resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400 IU (as interleukin-2 equivalent; 200 IU peritumorally, 200 IU perilymphatically) sequentially, daily 5 days/week for 3 weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Pre-surgery objective early response (45 objective early responders; 5 complete responses [CRs], 40 partial responses [PRs], confirmed by pathology at surgery. LI (+/- CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152-0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077-0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48-0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60 months, with 46.5 months median OS advantage (101.7 months vs. 55.2 months), respectively. Quality of life benefit for complete responders sustained for >3 years post LI treatment. Percent treatment-emergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.

新辅助白细胞介素注射免疫治疗可提高低风险局部晚期头颈部鳞状细胞癌的总生存率。
这项随机对照关键性 3 期研究评估了新辅助复合生物制剂白细胞介素注射液(LI)的疗效和安全性,该注射液在口腔和软腭局部晚期原发性鳞状细胞癌治疗前连续注射 3 周。以 3:1:3 随机分配到 LI+/-CIZ(环磷酰胺、吲哚美辛和锌)+SOC 或单独 SOC(标准治疗)。接受LI治疗的患者在手术前3周每天5天/周依次接受400 IU(相当于白细胞介素-2;瘤周200 IU,淋巴周围200 IU)。所有受试者均接受 SOC 治疗。手术后,复发风险低的患者将接受放疗,而风险高的患者则同时接受化放疗。中位随访时间为56个月。共有923名ITT(意向治疗)受试者(380名ITT低风险患者和467名ITT高风险患者)。手术前客观早期反应(45例客观早期反应者;5例完全反应[CR],40例部分反应[PR],经手术病理证实。LI(+/- CIZ)客观早期反应者占 8.5%(45/529 ITT),客观早期反应者占 16%(34/212 ITT 低风险),而 SOC 客观早期反应者无报告(0/394 ITT)。客观早期应答者将死亡率大幅降至22.2%(ITT LI治疗)和12.5%(ITT低风险LI + CIZ + SOC),而ITT低风险SOC死亡率为48.7%。因此,客观早期反应对总生存期(OS)有影响;ITT低风险LI治疗的比例危险比为0.348(95% CI:0.152-0.801),ITT低风险LI + CIZ + SOC的比例危险比为0.246(95% CI:0.077-0.787)。ITT 低风险 LI + CIZ + SOC 与 ITT 低风险 SOC 相比具有显著的 OS 优势(未分层对数rank p = 0.048;Cox 危险比 = 0.68;95% CI:0.48-0.95,Wald p = 0.024 [控制肿瘤分期、肿瘤位置和地理区域])。ITT低风险(LI + CIZ + SOC)治疗与ITT低风险SOC治疗的绝对OS优势随着时间的推移而增加:60个月时分别达到14.1%(62.7% vs. 48.6%)和46.5个月的中位OS优势(101.7个月 vs. 55.2个月)。完全应答者的生活质量获益在LI治疗后持续3年以上。所有治疗组的治疗突发不良事件百分比相当。手术后,LI 的安全性未超过单用 SOC 的安全性。NCT01265849, EUDRA:2010-019952-35.
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来源期刊
CiteScore
6.30
自引率
0.00%
发文量
134
审稿时长
4-8 weeks
期刊介绍: Pathology & Oncology Research (POR) is an interdisciplinary Journal at the interface of pathology and oncology including the preclinical and translational research, diagnostics and therapy. Furthermore, POR is an international forum for the rapid communication of reviews, original research, critical and topical reports with excellence and novelty. Published quarterly, POR is dedicated to keeping scientists informed of developments on the selected biomedical fields bridging the gap between basic research and clinical medicine. It is a special aim for POR to promote pathological and oncological publishing activity of colleagues in the Central and East European region. The journal will be of interest to pathologists, and a broad range of experimental and clinical oncologists, and related experts. POR is supported by an acknowledged international advisory board and the Arányi Fundation for modern pathology.
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