Ricciuti Biagio, Fusco Francesca, Cooper Alissa, Garbo Edoardo, Pecci Federica, Aldea Mihaela, Wang Xinan, Mayoral Penalva Maria, Ginsberg Michelle, Sholl Lynette M, Nishino Mizuki, Di Federico Alessandro, Shaverdian Narek, Bott Matthew, Santo Valentina, Rendina Erino, Trisolini Rocco, Ramella Sara, Gallina Filippo, Melis Enrico, Buglioni Simonetta, Minuti Gabriele, Landi Lorenza, Ugalde Figueroa Paula A, Shaw Alice T, Chaft Jamie, Awad Mark M, Cappuzzo Federico
Lowe Center of Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IRCCS Regina Elena National Cancer Institute, Rome, Italy.
JAMA Oncol. 2025 May 22. doi: 10.1001/jamaoncol.2025.1115.
Patients with borderline resectable or unresectable stage III non-small cell lung cancer (NSCLC) with T4 and/or N2-N3 involvement face limited treatment options and poor outcomes. Neoadjuvant chemoimmunotherapy has shown promise in improving resectability and pathological responses.
To evaluate the efficacy of neoadjuvant programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 (PD-L1) blockade combined with chemotherapy in enhancing surgical outcomes and pathological responses in patients with T4 and/or N2-N3 stage III NSCLC.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study analyzed data from patients treated between February 2018 and January 2024 with neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy at academic and tertiary care centers across the US and Italy. Pathological and survival outcomes were assessed. Patients with stage III NSCLC and T4 and/or N2-N3 involvement were included. Data were collected from February 2018 to January 2024.
Neoadjuvant PD-1/PD-L1 blockade combined with platinum-based chemotherapy.
Pathological complete response (pCR), major pathological response, surgical resectability, and event-free survival (EFS).
Of 112 patients, 58 (51.8%) were female, and the median (range) age was 66 (41-84) years. A total of 84(75.0%) underwent surgical resection, achieving a pCR rate of 29.0% (24 of 83 with available final pathology) and a major pathological response rate of 42.2% (35 of 83). Patients with both PD-L1 expression of 50% or more and high tumor mutational burden achieved the highest pCR rate (4 of 9 [44.4%]; P = .03). Conversely, covariants in KRAS/STK11 or KRAS/KEAP1 were associated with lack of pCR. Patients with single-station or multistation N2/N3 disease exhibited comparable pathological outcomes. The median EFS for all resected patients was 52.6 months (95% CI, 27.8 to not reached), and this was significantly longer in patients with pCR (not reached vs 27.8 months [95% CI, 19.5 to not reached]; P < .001).
In this study, neoadjuvant PD-1/PD-L1 blockade combined with chemotherapy resulted in high pathological response rates and surgical resectability in patients with T4 and/or N2-N3 stage III NSCLC. This approach offers a viable treatment option for patients with borderline resectable or unresectable NSCLC but requires further validation through prospective studies.
伴有T4和/或N2 - N3受累的临界可切除或不可切除的III期非小细胞肺癌（NSCLC）患者面临有限的治疗选择且预后较差。新辅助化疗免疫疗法在提高可切除性和病理反应方面已显示出前景。
评估新辅助程序性细胞死亡1蛋白（PD - 1）或程序性细胞死亡1配体1（PD - L1）阻断联合化疗在改善T4和/或N2 - N3期III期NSCLC患者手术结局和病理反应方面的疗效。
设计、地点和参与者：这项多中心队列研究分析了2018年2月至2024年1月期间在美国和意大利的学术及三级医疗中心接受新辅助PD - 1/PD - L1抑制剂加化疗的患者数据。评估了病理和生存结局。纳入了伴有III期NSCLC且T4和/或N2 - N3受累的患者。数据收集时间为2018年2月至2024年1月。
新辅助PD - 1/PD - L1阻断联合铂类化疗。
病理完全缓解（pCR）、主要病理反应、手术可切除性和无事件生存期（EFS）。
112例患者中，58例（51.8%）为女性，中位（范围）年龄为66（41 - 84）岁。共有84例（75.0%）接受了手术切除，pCR率为29.0%（83例有最终可用病理结果的患者中24例），主要病理反应率为42.2%（83例中的35例）。PD - L1表达≥50%且肿瘤突变负荷高的患者达到了最高pCR率（9例中的4例[44.4%]；P = 0.03）。相反，KRAS/STK11或KRAS/KEAP1的共变与未达到pCR相关。单站或多站N2/N3疾病的患者表现出相当的病理结局。所有切除患者的中位EFS为52.6个月（95%CI，27.8至未达到），pCR患者的EFS显著更长（未达到vs 27.8个月[95%CI，19.5至未达到]；P < 0.001）。
在本研究中，新辅助PD - 1/PD - L1阻断联合化疗在T4和/或N2 - N3期III期NSCLC患者中导致了高病理反应率和手术可切除性。这种方法为临界可切除或不可切除的NSCLC患者提供了一种可行的治疗选择，但需要通过前瞻性研究进一步验证。
