西班牙马德里马哈达翁达铁门大学医院Mariano Provencio团队研究了围手术期纳武单抗联合化疗对III期非小细胞肺癌患者预后的影响。相关论文发表在2023年6月28日出版的《新英格兰医学杂志》上。

大约20%的非小细胞肺癌（NSCLC）患者被诊断为III期疾病。对于这些患者最合适的治疗方法，目前尚未达成共识。

在这项开放标签的2期临床试验中，研究组随机分配可切除的IIIA或IIIB期NSCLC患者接受新辅助纳武单抗加铂类化疗（试验组）或单独化疗（对照组），然后进行手术。试验组中R0切除的患者接受了为期6个月的纳武单抗辅助治疗。主要终点是病理学完全缓解（切除的肺和淋巴结中有0%的肿瘤存活）。次要终点包括无进展生存率、24个月时的总生存率和安全性。

共有86名患者接受了随机分组；试验组57例，对照组29例。试验组37%的患者和对照组7%的患者出现病理学完全缓解（相对风险为5.34；P=0.02）。试验组93%的患者和对照组69%的患者进行了手术（相对风险为1.35）。Kaplan–Meier估计的24个月无进展生存率在试验组为67.2%，在对照组为40.9%（疾病进展、疾病复发或死亡的危险比为0.47）。Kaplan-Meier估计，试验组和对照组24个月时的总生存率分别为85.0%和63.6%（死亡风险比为0.43）。试验组11名患者（19%；一些患者同时发生2级不良事件）和对照组3名患者（10%）发生3级或4级不良事件。

研究结果表明，在可切除的IIIA或IIIB期NSCLC患者中，与单独化疗相比，纳武单抗加化疗的围手术期治疗导致病理学完全缓解的患者比例更高，生存期更长。

附：英文原文

Title: Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer

Author: Mariano Provencio, M.D., Ph.D.,, Ernest Nadal, M.D., Ph.D.,, José L. González-Larriba, M.D., Ph.D.,, Alex Martínez-Martí, M.D.,, Reyes Bernabé, M.D.,, Joaquim Bosch-Barrera, M.D.,, Joaquín Casal-Rubio, M.D.,, Virginia Calvo, M.D., Ph.D.,, Amelia Insa, M.D.,, Santiago Ponce, M.D., Ph.D.,, Noemí Reguart, M.D., Ph.D.,, Javier de Castro, M.D., Ph.D.,, Joaquín Mosquera, M.D., Ph.D.,, Manuel Cobo, M.D., Ph.D.,, Andrés Aguilar, M.D.,, Guillermo López Vivanco, M.D.,, Carlos Camps, M.D., Ph.D.,, Rafael López-Castro, M.D.,, Teresa Morán, M.D.,, Isidoro Barneto, M.D.,, Delvys Rodríguez-Abreu, M.D., Ph.D.,, Roberto Serna-Blasco, M.Sc.,, Raquel Benítez, Ph.D.,, Carlos Aguado de la Rosa, M.D.,, Ramón Palmero, M.D.,, Florentino Hernando-Trancho, M.D., Ph.D.,, Javier Martín-López, M.D.,, Alberto Cruz-Bermúdez, Ph.D.,, Bartomeu Massuti, M.D.,, and Atocha Romero, Pharm.D., Ph.D.

Issue&Volume: 2023-06-28

Abstract:

Background

Approximately 20% of patients with non–small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients.

Methods

In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety.

Results

A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P=0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan–Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan–Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%).

Conclusions

In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone.

DOI: 10.1056/NEJMoa2215530

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2215530