Department of Pulmonary Medicine, Amsterdam UMC Location VUmc, Amsterdam, Noord-Holland, Netherlands
Imaging and Biomarkers, Cancer Centre Amsterdam, Amsterdam, Noord-Holland, Netherlands.
J Immunother Cancer. 2024 Sep 30;12(9):e009799. doi: 10.1136/jitc-2024-009799.
In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC.
This single-arm, phase-II trial enrolled operable T3-4N0-2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy.
In a total of 30 patients in the intention-to-treat (ITT) population, grades 3-4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8 T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8CD39 T cells and lower HLA-DR Tregs.
Neoadjuvant IPI-NIVO-CRT in T3-4N0-2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs.
NCT04245514.
在非小细胞肺癌（NSCLC）中，放化疗（CRT）的病理完全缓解（pCR）率约为 30%。我们研究了在可切除和边界可切除的 NSCLC 中使用伊匹单抗联合纳武利尤单抗（IPI-NIVO）进行新辅助 CRT。
这是一项单臂、二期临床试验，招募了无致癌驱动因素的 IIIB-IV 期 T3-4N0-2 期 NSCLC 可手术患者。主要研究终点为安全性、主要病理缓解（MPR）和 pCR。治疗包括铂类双联 CRT 同步，第 1 天静脉注射 IPI 1mg/kg 和 NIVO 360mg，然后化疗加 NIVO 360mg 每 3 周静脉注射 1 次。胸部放疗为 50 或 60Gy，每日 2Gy 剂量。放疗后 6 周进行切除术。
在意向治疗（ITT）人群的 30 例患者中，3-4 级治疗相关不良事件（TRAEs）发生率为 70%，1 例 TRAE 级 5 例迟发性肺炎，发生在术后第 96 天（1/30，3.3%），1 例非 TRAE COVID-19 死亡（1/30，3.3%）。ITT 中的 pCR 和 MPR 分别为 50%（15/30）和 63%（19/30），26 例接受手术的患者分别为 58%（15/26）和 73%（19/26）。1 例非 pCR 患者术后出现黑色素瘤。R0 率为 100%（26/26），无患者因 TRAE 而手术失败。在外周血中，增殖性 CD8 T 细胞增加，而增殖性调节性 T 细胞（Tregs）没有增加。治疗期间，pCR 阳性患者的 CD8CD39 T 细胞更高，HLA-DR Tregs 更低。
在 T3-4N0-2 NSCLC 中，新辅助 IPI-NIVO-CRT 具有可接受的安全性，接受手术的患者中 pCR 和 MPR 分别为 58%和 73%。没有患者因 TRAE 而手术失败。
NCT04245514。
