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