PACIFIC Update Demonstrates Durvalumab OS Benefit For Stage III Inoperable NSCLC

Overall survival is longer with durvalumab than placebo for patients with unresectable stage III non-small-cell lung cancer that has not progressed after chemoradiation

medwireNews: Durvalumab significantly extends overall survival (OS) compared with placebo for patients with unresectable stage III non-small-cell lung cancer (NSCLC) that has not progressed after concurrent chemoradiation, research shows.
Initial findings from the PACIFC trial demonstrated a significant progression-free survival (PFS) benefit with the PD-L1 inhibitor, with a stratified hazard ratio (HR) for disease progression or death of 0.52, explain Scott Antonia, from the H Lee Moffit Cancer Center and Research Institute in Tampa, Florida, USA, and co-workers.
The team has now reported the secondary primary endpoint of OS at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto, Ontario, Canada, with a simultaneous publication in The New England Journal of Medicine.
At cutoff in March 2018, the trial participants had been followed-up for a median of 25.2 months; the 2-year OS rate was 66.3% for the 473 patients who were randomly assigned to receive durvalumab 10 mg/kg every 2 weeks versus 55.6% of the 236 placebo-treated controls, with a significant stratified HR for death of 0.68.
This OS was observed across all prespecified subgroups in the study based on patient characteristics, clinicopathology, and earlier response to treatment, the researchers emphasize.
PFS results were updated, to a median duration of 17.2 months for the durvalumab arm and 5.6 months for the placebo arm, with a stratified HR for disease or death of 0.52.
The frequency of new lesions was 22.5% for the durvalumab-treated patients and 33.8% for controls, with durvalumab associated with a reduced risk of new brain metastases, at 6.3% versus 11.8%.
Median time to death or distant metastases was 28.3 months for durvalumab-treated patients and 16.2 months for controls, a significant difference with a stratified HR of 0.53, the PACIFIC investigators continue. The corresponding values for median time to second progression or death was 28.3 months with durvalumab and 17.1 months with placebo (stratified HR=0.58).
The median duration of response for the durvalumab arm was unreached versus 18.4 months for those given placebo. Among responders, the response was ongoing at the 18-month checkpoint for 75.3% of patients using durvalumab and 52.2% of controls.
Scott Antonia and co-investigators say these findings “remain consistent with those that were previously reported and continue to show the substantial anticancer activity of durvalumab treatment in patients after induction therapy and its favorable effect on preventing metastatic spread, which may help to explain the observed survival benefit.”
Finally, the researchers report finding “no new safety signals”. Grade 3 or 4 adverse events occurred in 30.5% of the durvalumab arm and 26.1% of controls, with a corresponding 15.4% and 9.8% discontinuing treatment because of adverse events.
“These findings help to define the safety profile of durvalumab use after chemoradiotherapy, despite the trial being limited in its ability to distinguish or assign causality for some adverse events or to identify risk factors for their occurrence, owing to incomplete data regarding previous treatment”, they write.
Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC . N Engl J Med; Advance online publication 25 September 2018.
DOI: 10.1056/NEJMoa1809697

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