medwireNews: Consolidation treatment with the anti-programmed cell death ligand 1 (PD-L1) antibody durvalumab improves progression-free survival (PFS) in patients with stage III, locally advanced, inoperable non-small-cell lung cancer (NSCLC), shows the placebo-controlled PACIFIC trial.
The results of this prespecified interim analysis were presented at the ESMO 2017 Congress in Madrid, Spain, and simultaneously published in The New England Journal of Medicine.
A 700 person trial in a difficult group - we can do these trials.....and we are all very encouraged.
Watch an interview with Davey Daniel, one of the principal investigators of the study
The double-blind phase III trial enrolled 713 patients who had not progressed after definitive platinum-based chemoradiotherapy (≥2 cycles) and randomly allocated them to receive either durvalumab 10 mg/kg or placebo every 2 weeks for up to a year. The study treatment was given within 1–42 days after chemoradiation.
After a median follow-up of 14.5 months, the co-primary endpoint of PFS from randomization was significantly longer in the durvalumab than the placebo group, at a median of 16.8 and 5.6 months, respectively, equating to a significant hazard ratio (HR) for progression or death of 0.52.
The 12- and 18-month PFS rates in the durvalumab and placebo groups were 55.9% versus 35.3% and 44.2% versus 27.0%, respectively.
Luis Paz-Ares (Hospital Universitario Doce de Octubre, Madrid, Spain), who reported the results on behalf of the PACIFIC investigators, noted that the PFS benefit was maintained across all prespecified subgroups, including among patients with high (≥25%) or low (<25%) levels of PD-L1 expression.
He added that the data for the other primary endpoint of overall survival were not yet mature and that the study remained blinded for this endpoint.
In line with the PFS benefit, the team also observed improvements in other outcomes with durvalumab therapy. For instance, an objective response was achieved by 28.4% of durvalumab-treated participants and by 16.0% of those given placebo, a significant difference.
The duration of response was also longer with durvalumab than with placebo, with the median not reached in the durvalumab arm and 13.8 months in the placebo arm.
The safety profile of durvalumab was “quite favorable” and consistent with prior reports, the presenter commented, adding that “no new safety signals were identified.”
Adverse effects of grade 3 or 4 were observed in 29.9% of patients who received durvalumab and 26.1% of those treated with placebo. Pneumonia was the most frequent grade 3 or 4 toxicity in either arm, occurring in a respective 4.4% and 3.8% of participants, followed by pneumonitis (3.4%) in the durvalumab group and anemia (3.4%) in the placebo group.
Treatment was discontinued due to toxicity in 15.4% of patients in the durvalumab group and 9.8% of those in the placebo group.
Paz-Ares concluded that durvalumab has demonstrated a statistically significant and clinically relevant robust improvement in PFS over placebo, and that the overall survival findings are awaited.
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