Publication

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

Journal Paper/Review - Jul 12, 2021

Units
PubMed
Doi

Citation
Rothschild S, Cathomas R, Ochsenbein A, Janthur W, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M, Mark M, Peters S, Zippelius A, Eboulet E, Savic Prince S, Betticher D, Bettini A, Früh M, Jörger M, Lardinois D, Gelpke H, Mauti L, Britschgi C, Weder W, 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)
Journal
J Clin Oncol 2021; 39
Publication Date
Jul 12, 2021
Issn Electronic
1527-7755
Pages
2872-2880
Brief description/objective

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%.