Neoadjuvant chemotherapy plus durvalumab improves survival in resectable NSCLC

The addition of durvalumab to neoadjuvant chemotherapy with cisplatin and docetaxel results in better survival rates among patients with resectable nonsmall cell lung cancer (NSCLC), according to a study presented at ELCC 2025. 

“When compared to a pooled analysis of previous trials conducted by our working group using the same chemotherapy regimen, the addition of immunotherapy nearly doubled the 5-year event-free survival (EFS) and overall survival (OS) rates,” said lead author Dr Sacha Rothschild from Universitätsspital Basel, Basel, Switzerland. 

“It was particularly impressive in patients who achieved a major pathologic response (MPR) or pathologic complete response (pCR),” he added. 

Rothschild and his team conducted this multicentre, single-arm phase II trial (SAKK 16/14) to examine the benefit of perioperative treatment with durvalumab in addition to neoadjuvant chemotherapy with cisplatin and docetaxel, followed by surgery, in 68 patients with resectable stage IIIA NSCLC. Eligible patients received durvalumab postoperatively for a year. 

EFS at 1 year was the primary endpoint. The statistical hypothesis was based on an improvement in EFS from 48 percent to 65 percent. The study had a median follow-up of up to 72 months. 

SAKK 16/14 met its primary endpoint, with a 1-year EFS of 73 percent. Fifty-five patients (82 percent) underwent surgery, with 51 (93 percent) achieving an R0 resection. Thirty-one patients experienced an event as of 2 September 2024, with 25 progressions, three second tumours, and three deaths. [ELCC 2025, abstract 189MO] 

The median EFS stood at 4.0 years (95 percent confidence interval [CI], 2.4–not reached), with a 5-year EFS rate of 45.9 percent (95 percent CI, 31.7–59.0). Of the patients, 25 died during the study. The median OS was not reached, and the estimated OS rate was 65.8 percent (95 percent CI, 52.9–76.0) at 5 years. 

Pathologic response 

Thirty-four patients had an MPR (<10 percent viable tumour cells), while 10 (18 percent) achieved a pCR. Moreover, 37 participants (67 percent) had a postoperative nodal downstaging (ypN0-1). Patients who achieved a pCR had a 5-year OS rate of 100 percent, while those with an MPR had an OS rate of 97 percent. 

“The addition of perioperative durvalumab to standard of care cisplatin/docetaxel is safe, results in a very encouraging EFS and OS rate that exceeds historical data, [and] leads to high MPR rate and rate of nodal downstaging,” Rothschild said. 

Safety 

All patients (n=67) included in the safety analysis experienced at least one adverse event (AE), with the majority (n=59, 88.1 percent) having an AE grade ≥3 (neoadjuvant chemotherapy: n=45, 67.2 percent; neoadjuvant immunotherapy: n=8, 12.9 percent; surgery: n=17, 29.3 percent; adjuvant immunotherapy: n=25, 50.0 percent). 

Two patients experienced a fatal AE, specifically respiratory failure during neoadjuvant chemotherapy and bronchopulmonary haemorrhage after surgery, with a 30-day postoperative mortality rate of 1.8 percent. 

“To the best of our knowledge, this is the largest prospective trial to date investigating perioperative immunotherapy in patients with resectable NSCLC, with a follow-up period of 6 years,” Rothschild said.  

“The currently recruiting trial SAKK 16/18 is further exploring the potential benefit of immune-modulatory radiotherapy targeting the primary tumour,” he added.