Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO)

被引：72

作者：

Wislez, Marie ^{[1
]}

Mazieres, Julien ^{[2
]}

Lavole, Armelle ^{[3
]}

Zalcman, Gerard ^{[4
]}

Carre, Olivier ^{[5
]}

Egenod, Thomas ^{[6
]}

Caliandro, Raffaele ^{[7
]}

Dubos-Arvis, Catherine ^{[8
]}

Jeannin, Gaelle ^{[9
]}

Molinier, Olivier ^{[10
]}

Massiani, Marie-Ange ^{[11
]}

Langlais, Alexandra ^{[12
]}

Morin, Franck ^{[13
]}

Barthes, Francoise Le Pimpec ^{[14
]}

Brouchet, Laurent ^{[15
]}

Assouad, Jalal ^{[16
]}

Milleron, Bernard ^{[13
]}

Damotte, Diane ^{[17
]}

Antoine, Martine ^{[18
]}

Westeel, Virginie ^{[19
]}

机构：

[1] Univ Paris Cite, Pneumol, Hop Cochin, Assistance Publ Hop Paris APHP, Paris, France

[2] CHU Toulouse, Pneumol, Hop Larrey, Toulouse, France

[3] Univ Paris Cite, Hop Tenon, Pneumol, Paris, France

[4] Univ Paris Cite, Hop Bichat, Assistance Publ Hop Paris APHP, Thorac Oncol, Paris, France

[5] Clin Europe, Pneumol, Amiens, France

[6] Hop Dupuytren, Thorac Oncol, Limoges, France

[7] Inst Mutualiste Montsouris, Pneumol, Paris, France

[8] Ctr Francois Baclesse, Pneumol, Caen, France

[9] Hop Gabriel Montpied, Thorac Oncol, Clermont Ferrand, France

[10] Ctr Hosp Mans, Pneumol, Le Mans, France

[11] Hop Rene Huguenin, Med Oncol, Inst Curie, St Cloud, France

[12] French Cooperat Thorac Intergrp, Biostat, Paris, France

[13] French Cooperat Thorac Intergrp, Clin Res Unit, Paris, France

[14] Hop Europeen Georges Pompidou, Thorac Surg, Paris, France

[15] CHU Toulouse, Thorac Oncol, Hop Larrey, Toulouse, France

[16] Univ Paris Cite, Hop Tenon, Assistance Publ Hop Paris APHP, Thorac Surg, Paris, France

[17] Univ Paris Cite, Hop Cochin, Assistance Publ Hop Paris APHP, Pathol, Paris, France

[18] Univ Paris Cite, Hop Tenon, Pathol, Paris, France

[19] Hop Jean Minjoz, Pneumol, Besancon, France

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2022年 / 10卷 / 10期

关键词：

Immunotherapy; Lung Neoplasms; Biomarkers; Tumor; Programmed Cell Death 1 Receptor; SINGLE-ARM; OPEN-LABEL; ATEZOLIZUMAB; CHEMOTHERAPY;

D O I：

10.1136/jitc-2022-005636

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

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