Despite early cessation of the IFCT-1601 IONESCO study due to excessive early postoperative mortality, a 90% R0 rate was achieved following resection and neoadjuvant durvalumab therapy in patients with early stage resectable non-small cell lung cancer (NSCLC), according to findings presented by Marie Wislez of the Pneumo-Oncology, AP-HP Hôpital Cochin in Paris, France at the ESMO Virtual Congress 2020.
Dr Wislez and colleagues evaluated whether the immune checkpoint inhibitor, durvalumab, administered as preoperative therapy, could have benefit in early-stage NSCLC. They conducted the IFCT-1601 IONESCO multicentre study to assess the feasibility of neoadjuvant durvalumab.
Patients with IB lesions >4cm - IIIA, non N2, resectable NSCLC (TNM 8th edition) were treated with 3 courses of durvalumab at 750 mg on days 1, 15, 29 prior to resection, which was carried out between days 2 and 14 after the last infusion.
Of the 50 patients enrolled from April 2017 to August 2019, 46 were eligible. The patients had a median age of 61 years, 67.4% were males, 98% were smokers and all patients had ECOG performance score 0-1. Adenocarcinoma had been diagnosed in 25 patients and 19 had squamous cancer; 5, 14, 29, and 2 patient(s) had clinical stages IB, IIA, IIB, or IIIA.
Among the 46 eligible patients, 43 were operated (9 had pneumonectomy, 31 had lobectomy, 9 had bilobectomy) and 3 were not operated: one because of progression before surgery and 2 had an exploratory thoracotomy, (1 pleural carcinosis and 1 oesophageal invasion).
The primary endpoint of the study was the percent of complete surgical resection (R0), and secondary endpoints included safety, overall survival (OS), disease-free survival (DFS), time between first infusion and surgery, response rate per RECIST v1.1 and major pathological response (MPR).
Enrolment was halted early due to excessive 90-day mortality comprising 4 patients with extensive co-morbidities
This study was stopped due to an excess in 90-day postoperative mortality consisting of 4 (9%) deaths; of these, 1 patient died of acute respiratory failure, one of a surgical complication, one was due to tracheal fistula, and the cause was unknown in one patient who died at home. Of the 4 deceased patients, 3 had cardiovascular comorbidities consisting of 3 arterial hypertensions, one peripheral arterial disease and one ischemic heart disease or other co-morbidites that included one severe COPD and one diabetes. No Grades 3 to 5 durvalumab-related adverse events were observed.
The resected patients showed promising responses, R0 rates and 48-month survival
Following resection, 41 (90%) patients were R0.
Of 46 treated patients, 4 achieved partial response, 36 showed stable disease, and 6 patients experienced disease progression. Of the 6 progressions, one was a pseudoprogression.
The median time between first infusion and surgery was 37 days (range, 29 to 46 days).
Median OS and DFS were not reached. The 18-month OS rate was 89.1% (95% confidence interval [CI] 74.9-95.1) and the 18-month recurrence-free survival rate was 78.2% (95% CI 53.2-81.3).
Major pathological response (MPR) was observed in 8 patients (18.6%) with 3 patients in complete pathological response. MPR was associated with radiologic response (p = 0.028). The study investigators did not observe any death or recurrence in patients with MPR. Moreover, an association was observed between MPR and outcome (as shown in the figure), that was significant for DFS.
OS and DFS according to major pathological response: RVT, residual viable tumour cells; OS, overall survival; DFS, disease-free survival.
© Marie Wislez.
Conclusions
The authors noted that enrolment was stopped because of excessive 90-day postoperative mortality, but pointed out that these 4 deaths were due to postoperative complications that were possibly related to comorbidities and not to direct durvalumab toxicity. They observed a significant association between MPR and DFS.
This study was organised by French Cooperative Thoracic Intergroup (IFCT). Funding was reported from AstraZeneca.
Reference
1214O – Wislez M, Mazieres J, Lavole A, et al. Neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC): preliminary results from a multicenter study (IFCT-1601 IONESCO). ESMO Virtual Congress 2020.