■一些局部晚期(IIIA/IIIB)非小细胞肺癌(NSCLC)可能有手术选择。然而,关于新辅助免疫疗法治疗可能可切除的IIIA/IIIBNSCLC的有效性的信息有限.这项研究的目的是为可能可切除的III期NSCLC提供更有利的放化疗标准方法(同步或序贯放化疗),然后进行免疫治疗。
■这个前景,单臂,2期临床试验(NCT04326153)纳入了初次治疗的潜在可切除的IIIA/IIIBNSCLC患者,这些患者在初次诊断时被认为不适合完全(R0)切除.研究期间为2020年3月20日至2021年8月20日。在手术切除肺癌并在30-45天内进行系统性淋巴结清扫术之前,患者接受了新辅助化学免疫疗法(sintilimab联合nab-紫杉醇和卡铂)两到三个周期。主要终点是2年无病生存率(DFS),次要终点包括主要病理反应(MPR)率,病理完全缓解(pCR)率,总生存率,客观反应率(ORR),降级率,和不良事件(AE)。肿瘤免疫细胞浸润,通过免疫组织化学鉴定,在基线和手术后被评估为生物标志物。
■在接受新辅助化学免疫治疗的30名患者中,20例接受完全切除。疾病控制率为96.7%(95%CI:90.3%-99.99%),ORR为55%(95%CI:37.2%-72.8%),降级率为80%(95%CI:65.7%-94.3%)。在20名接受手术的患者的亚组中,MPR率为65%(95%CI:43.3%-82.9%),pCR率为40%(95%CI:21.2%-46.3%)。手术组的2年DFS率为75%(95%CI56%-94%)。值得注意的是,与非MPR组相比,MPR组DFS显著延长(p=0.00024).治疗前CD8表达的显著增加与改善的DFS相关(p=0.00019)。3例患者(10%)出现3级或更高的免疫相关不良事件-1例3级心肌酶升高,一例3级间质性肺炎,5级支气管胸膜瘘1例。
■新辅助免疫疗法显著提高了可能可切除的IIIA/IIIBNSCLC患者的病理反应率和2年DFS。治疗前CD8过表达(H评分≥3)可作为DFS的潜在预测生物标志物。因此,可能可切除的IIIA/IIIBNSCLC的治疗前景可能会发生变化.
■这项研究没有获得任何财政支持。
UNASSIGNED: Some locally advanced (IIIA/IIIB) non-small cell lung cancers (NSCLCs) might have surgical options available. However, information regarding the effectiveness of neoadjuvant immunotherapy for potentially resectable IIIA/IIIB NSCLC is limited. The intent of this investigation was to offer a more favourable alternative to the standard approach of chemoradiotherapy (concurrent or sequential chemoradiotherapy) followed by immunotherapy for potentially resectable stage III NSCLC.
UNASSIGNED: This prospective, single-arm, phase 2 clinical
trial (NCT04326153) enrolled treatment-naïve patients with \'potentially resectable\' IIIA/IIIB NSCLC who were deemed unsuitable for complete (R0) resection upon initial diagnosis. The
study period was between March 20, 2020, and August 20, 2021. Patients underwent neoadjuvant
chemoimmunotherapy (sintilimab combined with nab-paclitaxel and carboplatin) for two to three cycles prior to surgical resection of the lung carcinoma and systematic nodal dissection within 30-45 days. The primary endpoint was the 2-year disease-free survival (DFS) rate, with secondary endpoints encompassing major pathological response (MPR) rate, pathological complete response (pCR) rate, overall survival, objective response rate (ORR), downstaging rate, and adverse events (AEs). Tumour immune cell infiltrates, identified via immunohistochemistry, were assessed as biomarkers at baseline and after surgery.
UNASSIGNED: Among 30 patients who received neoadjuvant
chemoimmunotherapy, 20 underwent complete resection. The disease control rate was 96.7% (95% CI: 90.3%-99.99%), with an ORR of 55% (95% CI: 37.2%-72.8%) and a downstaging rate of 80% (95% CI: 65.7%-94.3%). In the subgroup of 20 patients who underwent surgery, the MPR rate was 65% (95% CI: 43.3%-82.9%), and the pCR rate was 40% (95% CI: 21.2%-46.3%). The 2-year DFS rate in the surgical group was 75% (95% CI 56%-94%). Notably, the MPR group demonstrated significantly prolonged DFS compared with the non-MPR group (p = 0.00024). A significant increase in pretreatment CD8 expression correlated with improved DFS (p = 0.00019). Three patients (10%) experienced grade 3 or higher immune-related AEs-one case of grade 3 elevated myocardial enzymes, one case of grade 3 interstitial pneumonia, and one case of grade 5 bronchopleural fistula.
UNASSIGNED: Neoadjuvant immunotherapy markedly enhanced the rate of pathological response and 2-year DFS in patients with potentially resectable IIIA/IIIB NSCLC. Overexpression of CD8 before treatment (H score≥3) may serve as a potential predictive biomarker for DFS. Consequently, the treatment landscape for potentially resectable IIIA/IIIB NSCLC could undergo changes.
UNASSIGNED: This
study did not receive any financial support.