Background Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients
with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine
benefits of both to improve long-term outcomes.Methods We randomly assigned patients
with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition
of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab
or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed
by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization
was stratified according to disease stage (II or III) and programmed death ligand
1 (PD-L1) expression (>= 1% or <1%). Primary end points were event-free survival (defined
as the time to the earliest occurrence of progressive disease that precluded surgery
or prevented completion of surgery, disease recurrence [assessed in a blinded fashion
by independent central review], or death from any cause) and pathological complete
response (evaluated centrally).Results A total of 802 patients were randomly assigned
to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free
survival was significantly longer with durvalumab than with placebo; the stratified
hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence
interval [CI], 0.53 to 0.88; P=0.004) at the first interim analysis. At the 12-month
landmark analysis, event-free survival was observed in 73.4% of the patients who received
durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received
placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was
significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final
analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim
analysis of data from 402 patients). Event-free survival and pathological complete
response benefit were observed regardless of stage and PD-L1 expression. Adverse events
of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2%
with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded
from the efficacy analyses in the modified intention-to-treat population.Conclusions
In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy
was associated with significantly greater event-free survival and pathological complete
response than neoadjuvant chemotherapy alone, with a safety profile that was consistent
with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number,
NCT03800134.)
