- A planned interim analysis of the PACIFIC trial has bolstered the PFS benefit of durvalumab in unresectable, stage III NSCLC, and has revealed clinically meaningful improvement in OS.
Why this matters
- The standard of care for unresectable, stage III NSCLC has been platinum-based chemoradiation.
- Outcomes are poor with such treatment, with only about 15%-30% of patients alive at 5 years.
- Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody developed as immunotherapy for NSCLC after chemoradiation therapy.
- The first interim analysis of the phase 3 PACIFIC trial (NCT02125461) reported improved PFS with durvalumab vs placebo.
- The latest results update PFS and secondary endpoints and provide the first data for the second primary endpoint of OS.
- Phase 3, randomized, double-blind, placebo-controlled, multicenter, international study.
- Patients with unresectable, stage III NSCLC without progression after platinum-based chemoradiation (n=713) were randomly assigned 2:1 to durvalumab (10 mg/kg every 2 weeks for up to 12 months; n=476) or to the same dose, schedule, and treatment length of placebo (n=237).
- Primary endpoints: PFS and OS.
- Key secondary endpoints: objective response rate, duration of response, median time to metastatic disease or death (TTDM), safety, and patient-reported outcomes.
- Funding: AstraZeneca.
- Published concurrent with publication in the New England Journal of Medicine.
- OS at 12 months: 83.1% in the durvalumab group, 75.3% in the placebo group.
- OS at 24 months: 66.3% in the durvalumab group, 55.6% in the placebo group.
- Median OS not reached in the durvalumab group (95% CI, 34.7 months-not reached), 28.7 months (95% CI, 22.9 months-not reached) in the placebo group.
- OS HR, 0.68 (99.73% CI, 0.469-0.997; P=.00251).
- PFS at 12 months: 55.7% in the durvalumab group, 34.4% in the placebo group.
- PFS at 24 months: 49.5% in the durvalumab group, 26.7%% in the placebo group.
- PFS HR, 0.51 (95% CI, 0.41-0.63).
- Median TTDM: 28.3 (95% CI, 24.0-34.9) months in the durvalumab group, 16.2 (95% CI, 12.5-21.1) months in the placebo group.
- TTDM HR, 0.53 (95% CI, 0.41-0.68).
- Durvalumab was well tolerated, with no new safety signals identified.
- No clear pattern of failure analysis.
- No mandatory biomarkers.
- Alternative strategies for patients with low expression of programmed death-ligand 1 need to be investigated.
- "PACIFIC is the first study to demonstrate a survival advantage for unresectable, stage III NSCLC, supporting the PACIFIC regimen of chemoradiation followed by durvalumab for up to 1 year as the standard of care," said presenter Scott J. Antonia, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.