IONESCO研究：多中心Ⅱ期IONESCO研究对IB（≥4cm）-ⅢA期非N2可切除的NSCLC（TNM第8版）患者术前给予3个周期的度伐利尤单抗，在此报告了DFS和OS与残余存活肿瘤细胞（RVT）之间的关联。
研究结果显示，患者的中位RVT为36.11%，中位OS 和DFS未达到。患者的18 个月OS和DFS分别为89.1%（95% CI，75.8-95.3）和73.7% （95% CI，58.4-84.1）。此外，多变量预后分析表明， 患者的RVT越高 ，其OS和DFS越差（OS HR，1.05；95% CI，1.00-1.10；p=0.04；DFS HR，1.06；95% CI，1.01-1.11]；p=0.02）[12]。
IONESCO 试验首次表明，在NSCLC 中，新辅助免疫治疗的病理反应是 OS 和 DFS 的独立预后因素。
Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO)
Background: The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC). Methods: In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131). Results: Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8-41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3-5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity. Conclusions: Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.
Wislez M, Mazieres J, Lavole A, Zalcman G, Carre O, Egenod T, Caliandro R, Dubos-Arvis C, Jeannin G, Molinier O, Massiani MA, Langlais A, Morin F, Le Pimpec Barthes F, Brouchet L, Assouad J, Milleron B, Damotte D, Antoine M, Westeel V. Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO). J Immunother Cancer. 2022 Oct;10(10):e005636. doi: 10.1136/jitc-2022-005636. PMID: 36270733; PMCID: PMC9594538.
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