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

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/m2 and docetaxel 85 mg/m2 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%.

Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer

“… 10 The recent published SAKK16/14 trial explored the additional benefit of two doses of durvalumab following three cycles of docetaxel plus cisplatin as neoadjuvant treatment in stage IIIA(N2) NSCLC, the MPR and pCR rates were 62% and 18%. 23 The best combination strategy of immunotherapy and chemotherapy, whether simultaneously or sequentially, warrants future investigation.…”

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer

“…A total of 4143 references were identified through the electronic search; 2914 potentially relevant articles remained for screening after the removal of duplicated studies. After applying the selection criteria, 33 studies remained for full assessment, and 18 publications from 16 studies were selected for quantitative analysis [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Two publications reported on the same trials with a focus on different clinical outcomes [6,7,12,13].…”

“…Two publications reported on the same trials with a focus on different clinical outcomes [6,7,12,13]. Eleven publications from nine studies were prospectively registered in national clinical trial registries [5][6][7][8][9][10][11][12][13][14][15]. There was one randomized controlled trial, which compared neoadjuvant nivolumab with nivolumab and ipilimumab prior to surgical resection [8].…”

“…Pathological response outcomes were reported as 'major pathological response' (MPR) when less than 10% of the viable tumor was identified in the primary lesion, and 'complete pathological response' (pCR) when no viable tumor was identified. However, some studies specifically reported pCR when both the primary lesion as well as the sampled lymph nodes were free from any viable tumor [5][6][7]9,10,[12][13][14]17,19,22], whereas others did not specify if nodal assessments were performed for pathological responses [8,11,15,16,18,20,21]. In addition, two studies defined MPR and pCR as being mutually exclusive, whereby patients who achieved a complete pathological response were not included within the group defined as a major pathological response [9,21].…”

What Is Neo? Chemoimmunotherapy in the Neoadjuvant Setting for Resectable Non–Small-Cell Lung Cancer

“…In the article that accompanies this editorial, Rothschild et al 3 report the results of a multicenter singlearm phase II trial that evaluated event-free survival (EFS) in patients with resectable stage IIIA (N2) NSCLC who underwent neoadjuvant treatment with cisplatin and docetaxel, followed by two doses of durvalumab, then surgical resection, and finally 1 year of durvalumab after surgery. The investigators capitalized on a robust foundation for neoadjuvant treatment, given their prior experience with other trials through the Swiss Group for Clinical Cancer Research (SAKK), including SAKK 16/96, 4 a neoadjuvant trial with cisplatin and docetaxel in stage IIIA (N2) disease and SAKK 16/00, 5 a randomized phase III study of neoadjuvant radiotherapy with chemotherapy.…”