Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO). Issue 10 (21st October 2022)

• Record Type: Journal Article
• Authors: Wislez, Marie; Mazieres, Julien; Lavole, Armelle; Zalcman, Gérard; Carre, Olivier; Egenod, Thomas; Caliandro, Raffaele; Dubos-Arvis, Catherine; Jeannin, Gaelle; Molinier, Olivier; Massiani, Marie-Ange; Langlais, Alexandra; Morin, Franck; Le Pimpec Barthes, Francoise; Brouchet, Laurent; Assouad, Jalal; Milleron, Bernard; Damotte, Diane; Antoine, Martine; Westeel, Virginie
• Is Part Of: Journal for immunotherapy of cancer. Volume 10:Issue 10(2022)
• Publication Date: 2022-10-21
• Subjects: Immunotherapy -- Lung Neoplasms -- Biomarkers, Tumor -- Programmed Cell Death 1 Receptor; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-005636
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.