背景：CheckMate816(NCT02998528)是对可切除的 NSCLC 中新辅助剂 NIVO 化疗与化疗的随机 3 期研究。该研究达到了第一个主要终点，证明新辅助 NIVO 化疗显著改善了病理完全反应(PCR)。这里我们报告了研究的关键手术结果。

Background: CheckMate 816 (NCT02998528) is a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo in resectable NSCLC. The study met its first primary endpoint, demonstrating significantly improved pathological complete response (pCR) with neoadjuvant NIVO + chemo. Here we report key surgical outcomes from the study.

方法：将 IB 期（≥4cm）-IIIA（按 AJCC 第 7 版）可切除 NSCLC、ECOG PS≤1 且未发生已知 EGFR/ALK 改变的成人随机分配到 NIVO 360mg 铂双态化疗 Q3W 或化疗 Q3W 进行 3个周期（分别 n=179）。最终的手术将在治疗后的 6 周内进行。主要终点为 pCR（定义为肺和淋巴结中 0%可行的肿瘤细胞）和无事件生存率；两者均通过盲法独立审查进行评估。手术和手术相关不良事件(AE)的可行性是探索性终点。

Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ALK alterations were randomized to NIVO 360 mg + platinum-doublet chemo Q3W or chemo Q3W for 3 cycles (n = 179 each). Definitive surgery was to be performed within 6 weeks of treatment. Primary endpoints are pCR (defined as 0% viable tumor cells in lung and lymph nodes) and event-free survival; both are evaluated by blinded independent review. Feasibility of surgery and surgery-related adverse events (AEs) are exploratory endpoints.

结果：两组间的基线特征相似，64%的患者(患者)为 IIIA 期。NIVO 化疗时（n=149）的最终手术率为 83%，而化疗时为 75%（n=135）。导致手术取消的原因是疾病进展（分别为12 和 17 患者）、不良事件（2 患者/arm）或其他情况（分别为 14 和 19 患者；包括患者拒绝、不可切除、肺功能差）。微创手术率分别为 30%和 22%，NIVO 化疗和化疗从微创手术率转换到开放手术率分别为 11%和 16%。77%和 61%的患者分别进行了肺切除术，NIVO 化疗的肺切除术分别为 17%和 25%的肺切除术。不良事件导致 NIVO 化疗组 6 例和化疗组 9 例的手术延迟。83%对 78%的患者进行 R0 切除，NIVO 化疗组的中位剩余存活肿瘤(RVT)细胞为 10%和 74%。NIVO 化疗与化疗期间的中位数（Q1、Q3）手术时间和住院时间没有增加（184vs217min；分别为 10.0vs10.0 天）。NIVO 化疗和 4 级手术相关不良事件和 11%分别为 41%和 47%和 15%。在 NIVO 化疗组和化疗组中，有 2vs0 患者报告了 5 级手术相关不良事件；0vs3 患者分别死于治疗相关不良事件。

Results: Baseline characteristics were comparable between arms; 64% of patients (pts) were stage IIIA. Definitive surgery rates were 83% with NIVO + chemo (n = 149) vs 75% with chemo (n = 135). Reasons for cancelled surgery were disease progression (12 and 17 pts, respectively), AEs (2 pts/arm), or other scenarios (14 and 19 pts, respectively; including pt refusal, unresectability, poor lung function). Minimally invasive surgery rates were 30% and 22%, and conversion from minimally invasive to open surgery rates were 11% and 16% for NIVO + chemo and chemo, respectively. Lobectomy was performed in 77% vs 61% of pts, and pneumonectomy in 17% and 25% for NIVO + chemo vs chemo, respectively. AEs were responsible for delays of surgery in 6 pts in the NIVO + chemo arm and 9 pts in the chemo arm. An R0 resection was achieved in 83% vs 78% of pts and median residual viable tumor (RVT) cells in the primary tumor bed were 10% vs 74% for NIVO + chemo vs chemo. There was no increase in median (Q1, Q3) duration of surgery and length of hospitalization between NIVO + chemo vs chemo (184 [130, 252] vs 217 [150, 283] min; and 10.0 [7, 14] vs 10.0 [7, 14] days, respectively). Any-grade and grade 3–4 surgery-related AEs were reported in 41% vs 47% and 11% vs 15% of the NIVO + chemo vs chemo arms, respectively. Grade 5 surgery-related AEs were reported in 2 vs 0 pts in the NIVO + chemo vs chemo arms; 0 vs 3 pts died due to treatment-related AEs, respectively.

结论：在CheckMate816 中，新辅助 NIVO 化疗不妨碍手术的可行性和时间，以及切除与单独化疗的程度或完整性，治疗可接受，不增加手术并发症。NIVO 化疗导致了病理反应的深度的增加。CheckMate816 的手术结果数据，作为 IB-IIIA 切除 NSCLC 患者的潜在新辅助选择。

Conclusions: In CheckMate 816, neoadjuvant NIVO + chemo did not impede the feasibility and timing of surgery, nor the extent or completeness of resection vs chemo alone; treatment was tolerable and did not increase surgical complications. NIVO + chemo led to increased depth of pathological response. The surgical outcome data from CheckMate 816 along with significant improvement in pCR support NIVO + chemo as a potential neoadjuvant option for patients with stage IB to IIIA resectable NSCLC.