新辅助纳武利尤单抗联合化疗治疗可切除肺癌。
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.
机构信息
From the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore (P.M.F., S.R.B., J.R.B., J.M.T.); McGill University Health Center (J.S.), and Centre Hospitalier de l'Université de Montréal (M.L.) - both in Montreal; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin (C.W.), and Peking University School of Oncology, Beijing Cancer Hospital, Beijing (K.-N.C.) - all in China; Hospital Universitario Puerta de Hierro, Madrid (M.P.); Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama (T.M.), the University of Occupational and Environmental Health, Kitakyushu (F.T.), and Kanagawa Cancer Center, Yokohama (H.I.) - all in Japan; Dana-Farber Cancer Institute, Boston (M.M.A., S.J.S.); Vall d'Hebron Institute of Oncology, Barcelona (E.F.); Aberdeen Royal Infirmary, Aberdeen, United Kingdom (K.K.); Institutul Oncologic Prof. Dr. Ion Chiricuta and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Charleston Oncology, Charleston, SC (G.B.S.); University of Chicago Medicine, Chicago (E.E.V.); Bristol Myers Squibb, Princeton, NJ (C.D., J.C., J.F., A.J., D.B., M.S., D.P., C.Y.C.); and Institut du Thorax Curie-Montsouris, Institut Curie, Paris (N.G.).
出版信息
N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.
BACKGROUND
Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.
METHODS
In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.
RESULTS
The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.
CONCLUSIONS
In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).
背景
新辅助或辅助化疗在可切除的非小细胞肺癌（NSCLC）中比单纯手术有一定的获益。在早期临床试验中，基于纳武利尤单抗的新辅助方案显示出有希望的临床活性；然而，需要来自 3 期试验的数据来证实这些发现。
方法
在这项开放标签的 3 期临床试验中，我们将 IB 期至 IIIA 期可切除 NSCLC 患者随机分配接受纳武利尤单抗联合铂类化疗或单纯铂类化疗，然后进行切除。主要终点是无事件生存和病理完全缓解（切除肺和淋巴结中无存活肿瘤的 0%），均通过盲法独立评估。总生存是一个关键次要终点。所有接受治疗的患者均进行安全性评估。
结果
纳武利尤单抗联合化疗组的中位无事件生存期为 31.6 个月（95%置信区间[CI]，30.2 至未达到），化疗组为 20.8 个月（95%CI，14.0 至 26.7）（疾病进展、复发或死亡的风险比为 0.63；97.38%CI，0.43 至 0.91；P=0.005）。病理完全缓解的患者比例分别为 24.0%（95%CI，18.0 至 31.0）和 2.2%（95%CI，0.6 至 5.6）（比值比为 13.94；99%CI，3.49 至 55.75；P<0.001）。在大多数亚组中，无事件生存和病理完全缓解的结果均表明纳武利尤单抗联合化疗优于单纯化疗。在首次预设的中期分析中，死亡的风险比为 0.57（99.67%CI，0.30 至 1.07），未达到显著性标准。接受随机分组的患者中，纳武利尤单抗联合化疗组的 83.2%和单纯化疗组的 75.4%接受了手术。纳武利尤单抗联合化疗组和单纯化疗组分别有 33.5%和 36.9%的患者发生 3 级或 4 级治疗相关不良事件。
结论
在可切除的 NSCLC 患者中，新辅助纳武利尤单抗联合化疗与单纯化疗相比，显著延长了无事件生存时间，且病理完全缓解的患者比例更高。纳武利尤单抗联合新辅助化疗并未增加不良事件的发生率或妨碍手术的可行性。（由 Bristol Myers Squibb 资助；CheckMate 816 临床试验.gov 编号，NCT02998528.）。
Zotero 插件