新辅助免疫疗法联合化疗可改善无事件生存期 (EFS) 和病理完全缓解（pCR、原发肿瘤 [PT] 淋巴结 [LN] 中残留存活肿瘤 [RVT] 为 0%），并被批准用于治疗可切除肺癌。新辅助治疗后的病理反应评估可能类似于晚期疾病的放射学反应。然而，尚未探讨超出 pCR 和主要病理反应 (≤10% RVT) 的 %RVT 阈值。在随机 3 期 CheckMate 816 试验 (NCT02998528) 中对病理反应进行了前瞻性评估，该试验评估了可切除肺癌患者的新辅助纳武单抗（抗 PD-1）加化疗。使用泛肿瘤评分系统对 PT 和 LN 中的 RVT、消退和坏死进行量化（0%-100%），并在预先指定的探索性分析中测试与 EFS 的关联。无论 LN 是否受累，EFS 均以 0% 与 RVT-PT >0% 改善 (HR = 0.18)。 RVT-PT 预测纳武单抗联合化疗的 EFS（AUC = 0.74）； RVT 为 0%-5%、>5%-30%、>30%-80% 和 >80% 的患者的 2 年 EFS 率分别为 90%、60%、57% 和 39%。每 1% RVT 与 EFS 增加 0.017 HR 相关。结合 PT LN 的病理反应有助于区分结果。与放射学反应和 ctDNA 清除率相比，%RVT 最接近 EFS。这些发现支持病理反应作为新兴的生存替代指标。有必要对肺癌和其他肿瘤类型的 %RVT 全谱进行进一步评估。© 2023。作者获得 Springer Nature America, Inc. 的独家许可。

Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (pCR, 0% residual viable tumor [RVT] in primary tumor [PT]+lymph nodes [LNs]), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pCR and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-PD-1) plus chemotherapy in patients with resectable lung cancer. RVT, regression, and necrosis were quantified (0%-100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus >0% RVT-PT (HR = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (AUC = 0.74); 2-year EFS rates were 90%, 60%, 57%, and 39% for patients with 0%-5%, >5%-30%, >30%-80%, and >80% RVT, respectively. Each 1% RVT associated with a 0.017 HR increase for EFS. Combining pathologic response from PT+LNs helped differentiate outcomes. When compared to radiographic response and ctDNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.