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Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer
Mark M. Awad, Patrick M. Forde, Nicolas Girard, et al. Journal of Clinical Oncology. January 8, 2025
目的：新辅助免疫检查点抑制剂纳武利尤单抗联合伊匹木单抗可提高非小细胞肺癌（NSCLC）患者的总生存期（OS）；然而，针对可切除肺癌的随机数据有限。我们报告了国际 III 期 CheckMate 816 试验中纳武利尤单抗联合伊匹木单抗与化疗的探索性随机分组研究结果。
方法：患有 IB - IIIA 期（美国癌症联合委员会第七版）可切除 NSCLC 的成年人接受三个周期的纳武利尤单抗（每 2 周一次）加一个周期的伊匹木单抗治疗，或三个周期的化疗（每个 3 周周期的第 1 天或第 1 天和第 8 天），随后进行手术。分析包括无事件生存期（EFS）、OS、病理缓解情况、手术结果、生物标志物分析和安全性。
结果：共有 221 名患者被随机分配接受纳武利尤单抗联合伊匹木单抗（n = 113）或化疗（n = 108）。中位随访时间为 49.2 个月时，纳武利尤单抗联合伊匹木单抗组的中位 EFS 为 54.8 个月（95% 置信区间，24.4 至未达到 [NR]），而化疗组为 20.9 个月（95% 置信区间，14.2 至 NR）（风险比 [HR]，0.77 [95% 置信区间，0.51 至 1.15]）；3 年 EFS 率分别为 56% 和 44%。最初观察到 EFS 事件发生率较高，但后期纳武利尤单抗联合伊匹木单抗组更具优势；3 年 OS 率分别为 73% 和 61%（HR，0.73 [95% 置信区间，0.47 至 1.14]）；病理完全缓解率分别为 20.4% 和 4.6%。在各自的治疗组中，分别有 83 例（74%）和 82 例患者（76%）接受了根治性手术。3 - 4 级治疗相关不良事件分别发生在 14% 和 36% 的患者中。
结论：新辅助纳武利尤单抗联合伊匹木单抗相较于化疗显示出潜在的长期临床益处，尽管在术前阶段 EFS 曲线早期交叉且高级别毒性发生率较低。
Purpose: Neoadjuvant immune checkpoint blockade with nivolumab plus ipilimumab improves overall survival (OS) in non–small cell lung cancer (NSCLC); however, randomized data for resectable lung cancer are limited. We report results from the exploratory concurrently randomized nivolumab plus ipilimumab and chemotherapy arms of the international phase III CheckMate 816 trial.
Methods: Adults with stage IB-IIIA (American Joint Committee on Cancer seventh edition) resectable NSCLC received three cycles of nivolumab once every 2 weeks plus one cycle of ipilimumab or three cycles of chemotherapy (on day 1 or days 1 and 8 of each 3-week cycle) followed by surgery. Analyses included event-free survival (EFS), OS, pathologic response, surgical outcomes, biomarker analyses, and safety.
Results: A total of 221 patients were concurrently randomly assigned to nivolumab plus ipilimumab (n = 113) or chemotherapy (n = 108). At a median follow-up of 49.2 months, the median EFS was 54.8 months (95% CI, 24.4 to not reached [NR]) with nivolumab plus ipilimumab versus 20.9 months (95% CI, 14.2 to NR) with chemotherapy (HR, 0.77 [95% CI, 0.51 to 1.15]); 3-year EFS rates were 56% versus 44%. Higher rates of EFS events were initially seen, with later benefit favoring nivolumab plus ipilimumab; 3-year OS rates were 73% versus 61% (HR, 0.73 [95% CI, 0.47 to 1.14]); pathologic complete response rates were 20.4% versus 4.6%, respectively. In the respective arms, 83 (74%) and 82 patients (76%) underwent definitive surgery. Grade 3-4 treatment-related adverse events occurred in 14% and 36% of patients, respectively.
Conclusions: Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit versus chemotherapy, despite early crossing of EFS curves in the preoperative phase and a lower rate of high-grade toxicity.
Context Key Objective
Dual immunotherapy has demonstrated long-term survival benefit in patients with metastatic non–small cell lung cancer (NSCLC) and promising clinical activity as neoadjuvant treatment in patients with resectable disease. This exploratory analysis from the phase III CheckMate 816 trial evaluated the efficacy and safety of neoadjuvant nivolumab plus ipilimumab versus chemotherapy in patients with stage IB-IIIA resectable NSCLC.
Neoadjuvant nivolumab plus ipilimumab showed trends toward improved survival and higher pathologic complete response rates versus chemotherapy. The safety profile of neoadjuvant nivolumab plus ipilimumab was consistent with previous reports in NSCLC, with low rates of high-grade toxicity.
Despite the activity observed with nivolumab and ipilimumab in this exploratory analysis the higher rate of early event-free survival events preclude its use in routine clinical care. Additional studies are needed to refine the patient population.*
CheckMate 816：新辅助纳武利尤单抗+化疗治疗可切除非小细胞肺癌
CheckMate 816：研究设计
参考文献：
Awad, M. M., Forde, P. M., Girard, N., Spicer, J., Wang, C., Lu, S., Mitsudomi, T., Felip, E., Broderick, S. R., Swanson, S. J., Brahmer, J., Kerr, K., Saylors, G. B., Chen, K. N., Gharpure, V., Neely, J., Balli, D., Hu, N., & Provencio Pulla, M. (2025). Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer. Journal of Clinical Oncology, 43(12), 1453-1462. https://doi.org/10.1200/JCO-24-02239
Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer | Journal of Clinical Oncology
US Food and Drug Administration Approval Summary: Nivolumab Plus Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With Resectable Non–Small-Cell Lung Cancer | Journal of Clinical Oncology
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