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SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial

Sacha I Rothschild, Alfred Zippelius, Eric I Eboulet, Spasenija Savic Prince, Daniel Betticher, Adrienne Bettini, Martin Früh, Markus Joerger, Didier Lardinois, Hans Gelpke, Laetitia A Mauti, Christian Britschgi, Walter Weder, Solange Peters, Michael Mark, Richard Cathomas, Adrian F Ochsenbein, Wolf-Dieter Janthur, Christine Waibel, Nicolas Mach, Patrizia Froesch, Martin Buess, Pierre Bohanes, Gilles Godar, Corinne Rusterholz, Michel Gonzalez, Miklos Pless & Swiss Group For Clinical Cancer Research (SAKK)

abstract

PURPOSE
For patients with resectable stage IIIA(N2) non-small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab.

METHODS
Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m and docetaxel 85 mg/m once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%.

RESULTS
Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related.

CONCLUSION
The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.
   
citation Rothschild S I, Zippelius A, Eboulet E I, Savic Prince S, Betticher D, Bettini A, Früh M, Joerger M, Lardinois D, Gelpke H, Mauti L A, Britschgi C, Weder W, Peters S, Mark M, Cathomas R, Ochsenbein A F, Janthur W D, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M, Swiss Group For Clinical Cancer Research (SAKK) . SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol 2021; 39:2872-2880.
   
type journal paper/review (English)
date of publishing 12-07-2021
journal title J Clin Oncol (39/26)
ISSN electronic 1527-7755
pages 2872-2880
PubMed 34251873
DOI 10.1200/JCO.21.00276