Consolidation therapy with durvalumab provided a robust and sustained overall survival (OS) and durable progression-free survival (PFS) benefit compared with placebo in patients with unresectable, stage III non-small cell lung cancer (NSCLC), according to researchers.

Approximately 43% of patients treated with durvalumab remained alive at 5 years, and 33% of patients remained free from disease progression. This establishes a new benchmark for the standard of care in this setting, according to researchers.

The researchers reported these results, from the phase 3 PACIFIC trial, in the Journal of Clinical Oncology. 


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In the double-blind, placebo-controlled PACIFIC trial (ClinicalTrials.gov Identifier: NCT0212546), researchers compared durvalumab with placebo in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy.

The multicenter study enrolled 713 patients, 476 of whom were randomly assigned to receive durvalumab and 237 to receive placebo. Patients were stratified by age, sex, and smoking history.

In an earlier analysis, consolidation durvalumab was associated with a significant improvement in OS (hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P =.00251) and PFS (HR, 0.52; 95% CI, 0.42-0.65; P <.0001).

As of January 11, 2021, the median follow-up was 34.2 months (range, 0.2-74.7 months) for all randomly assigned patients and 61.6 months (range, 0.4-74.7 months) for patients last known to be alive.

The updated 5-year OS and PFS outcomes remained consistent with the primary analysis and continued to favor durvalumab over placebo.

The updated OS analysis showed a 28% reduction in the risk of death with durvalumab compared with placebo (HR, 0.72; 95% CI, 0.59-0.89). The median OS was 47.5 months in the durvalumab arm and 29.1 months in the placebo arm. The estimated 5-year OS rates in the durvalumab and placebo arms were 42.9% and 33.4%, respectively.

The updated PFS analysis showed a 45% reduction in the risk of disease progression or death with durvalumab compared with placebo (HR, 0.55; 95% CI, 0.45-0.68). The median PFS was 16.9 months with durvalumab and 5.6 months with placebo. The estimated 5-year PFS rates in the durvalumab and placebo arms were 33.1% and 19.0%, respectively. 

The researchers noted a 41% reduction in the risk of death or distant metastasis among patients treated with durvalumab compared with placebo (HR, 0.59; 95% CI, 0.47-0.74). The overall response rate was higher among patients treated with durvalumab (29.8%) compared with those who received placebo (18.3%).

Subsequent immunotherapy was less frequently used among patients in the durvalumab arm (12.6%) compared with those in the placebo arm (29.1%).

The OS and PFS benefit favored durvalumab over placebo across all PD-L1 subgroups, with the exception of OS in patients with PD-L1 expression less than 1% (HR, 1.15; 95% CI, 0.75-1.75).

“These updated survival analyses demonstrate robust and sustained survival benefit with durvalumab after [chemoradiotherapy],” the researchers wrote. “The findings support the continued use of consolidation durvalumab after chemoradiotherapy as the standard of care for patients with unresectable, stage III non-small cell lung cancer.”

Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. Published online January 2, 2022. doi:10.1200/JCO.21.01308