Henick Brian S, Koch Peter D, Gainor Justin F, Awad Mark M, Chiuzan Codruta, Izard Stephanie, Georgis Yohanna, Mallick Samyukta, Garofano Robert F, Wong Cheryl V, Saqi Anjali, Grindheim Jessica, Schulze Katja, Sonett Joshua R, Rizvi Naiyer A, Izar Benjamin, Taylor Alison M, Shu Catherine A
Department of Medicine, Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York, USA
Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
J Immunother Cancer. 2024 Dec 25;12(12):e009301. doi: 10.1136/jitc-2024-009301.
Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.
This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers.
Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in and did not have a significantly higher incidence of BM. Reduced copy number of and , both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of was significantly associated with worse pathological response and incidence of BM.
Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between and genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.
新辅助化疗免疫疗法已使可切除的非小细胞肺癌（NSCLC）患者的总生存期（OS）受益。在此，我们展示了新辅助阿替利珠单抗联合化疗的首次报道研究随访3年后的结果。
这项开放标签、多中心单臂研究者发起的II期研究在美国的三家医院进行，在手术前测试了多达四个周期的阿替利珠单抗、卡铂和白蛋白结合型紫杉醇。主要病理缓解（MPR，主要终点）此前已有报道；在此，我们报告3年无病生存期（DFS）、OS，以及通过肿瘤基因组学、基因表达和免疫标志物定量免疫荧光测量的综合数据得出的发生脑转移（BM）患者的临床特征。
30名入组患者中，29名接受了手术。26名患者进行了R0切除，其中17名达到MPR（10名达到病理完全缓解）。中位随访39.5个月，中位OS为55.8个月，中位DFS为34.5个月。36个月时的OS里程碑为77%。在14名复发患者中，6名患者发生了BM。肿瘤发生 和 突变的患者BM发生率没有显著更高。在约1/3的肿瘤中观察到位于19号染色体短臂上的 和 的拷贝数减少。 的拷贝数减少与更差的病理反应和BM发生率显著相关。
与近期的III期研究一致，新辅助阿替利珠单抗联合化疗的3年OS数据与延长的无进展生存期（PFS）和OS相关。在早期NSCLC中建立 和 基因组改变与关键临床结果之间的关联需要进一步研究。
