Durable “robust” Durvalumab OS consolidation, benefit of PFS in NSCLC
According to the researchers, consolidation therapy with durvalumab provided a robust and sustained advantage in terms of overall survival (OS) and durable progression-free survival (PFS) compared to placebo in patients with lung cancer not unresectable stage III small cell tumor (NSCLC).
Approximately 43% of patients treated with durvalumab remained alive at 5 years, and 33% of patients remained without disease progression. This sets a new benchmark for the standard of care in this setting, the researchers say.
The researchers reported these results, from the Phase 3 PACIFIC trial, in the Journal of Clinical Oncology.
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, of whom 476 were randomized to receive durvalumab and 237 to receive placebo. Patients were stratified by age, sex, and smoking history.
In a previous analysis, consolidation durvalumab was associated with a significant improvement in OS (relative risk [HR], 0.68; 95% CI, 0.53-0.87; P = 0.00251) 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 the last known living patients.
Updated 5-year OS and PFS results remained consistent with the primary analysis and continued to favor durvalumab over placebo.
The updated OS analysis showed a 28% reduced risk of death with durvalumab compared to 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 to placebo (HR, 0.55; 95% CI, 0.45-0.68 ). 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 metastases in patients treated with durvalumab compared to placebo (HR, 0.59; 95% CI, 0.47-0.74). The overall response rate was higher in patients treated with durvalumab (29.8%) than in those who received placebo (18.3%).
Subsequent immunotherapy was used less frequently in patients in the durvalumab arm (12.6%) than in those in the placebo arm (29.1%).
The benefit of OS and PFS favored durvalumab over placebo in all PD-L1 subgroups, except for OS in patients with PD-L1 expression less than 1% (HR , 1.15; 95% CI, 0.75-1.75).
“These updated survival analyzes demonstrate a robust and durable survival benefit with durvalumab after [chemoradiotherapy]”, wrote the researchers. “The results 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 funded by AstraZeneca. Some study authors have declared affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original reference for a full list of disclosures.
Spigel DR, Faivre-Finn C, Gray JE, et al. Five-Year Survival Results 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