PACIFIC
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Clinical Question
In patients with unresectable stage 3 non-small-cell lung cancer (NSCLC) who completed platinum-based chemoradiotherapy, does durvalumab as a consolidation therapy improve survival compared to placebo?
Bottom Line
Among patients with unresectable stage 3 non-small-cell lung cancer (NSCLC) who have completed definitive chemoradiotherapy, consolidation immunotherapy with durvalumab improved progression-free survival when compared to placebo.
Major Points
Definitive therapy with platinum-based chemoradiotherapy had been the standard of care for patients with unresectable, locally advanced NSCLC. Nevertheless, the prognosis of this group of patients has been poor, with median progression-free survival (PFS) of under one year.[1]. Meanwhile, checkpoint inhibitors including durvalumab, have demonstrated efficacy in patients with metastatic disease. A trial investigating the efficacy of immunotherapy consolidation after primary chemoradiotherapy was needed for this cohort of patients.
The PACIFIC trial enrolled patients with unresectable, locally advanced stage 3 NSCLC who had not progressed after 2 cycles of platinum-based chemoradiotherapy. Some 700 patients were randomized 2:1 to durvalumab or placebo, and received up to one year of biweekly therapy. Patients were followed and evaluated for the coprimary endpoints of PFS and overall survival (OS). At a median follow-up of 14.5 months, the durvalumab group had improved PFS (16.8 vs. 5.6 months).
Guidelines
NCCN Guidelines Non-Small-Cell Lung Cancer (4.2025, adapted)[2]
- Durvalumab is recommended as a consolidation immunotherapy option (regardless of PDL1 status) for patients with unresectable stage 3 NSCLC and without disease progression after treatment with definitive concurrent platinum-based chemoradiation (Category 1)
Design
- Multicenter, randomized controlled trial.
- N=709 patients with unresectable locally advanced stage 2-3 NSCLC
- Darvulumab (n=473)
- Placebo (n=256)
- Setting: Multicenter
- Enrollment: 2014-2016
- Median follow-up: 14.5 months
- Analysis: Intention-to-treat
- Primary outcome: Progression-free survival and overall survival
Population
Inclusion Criteria
- Unresectable, locally advanced stage 3 (some stage 2 included) NSCLC
- Received two or more cycles (defined according to local practice) of platinum-based chemotherapy (containing etoposide, vinblastine, vinorelbine, a taxane [paclitaxel or docetaxel], or pemetrexed)
- Concurrent definitive radiation therapy (54 to 66 Gy)
- No disease progression following concurrent chemoradiotherapy
- WHO Performance status 0 or 1
- Age ≥18 years
Exclusion Criteria
- Previous exposure to anti–PD-1 or PD-L1 antibodies
- Any receipt of immunotherapy or an investigational drug within 4 weeks before the first dose (6 weeks for monoclonal antibodies)
- Active or previous autoimmune disease (within the past 2 years)
- History of primary immunodeficiency or evidence of uncontrolled, concurrent illness or ongoing or active infections
- Unresolved toxic effects of grade 2 or higher and grade 2 or higher pneumonitis from previous chemoradiotherapy.
Baseline Characteristics
- Mean age: 64 years
- Male: 70.1%
- Stage
- IIIA: 52.9%
- IIIB: 44.7%
- Other: 2.4%
- Histology
- Squamous: 45.7%
- Non-squamous: 54.3%
- Smoking Status
- Current: 16.4%
- Former: 74.6%
- Never: 9.0%
Interventions
- Patients were randomized to durvalumab (10 mg/kg IV) or matching placebo beginning 1 to 42 days following chemoradiotherapy.
- Patients received durvalumab or placebo every 2 weeks for up to 12 months.
Outcomes
Comparisons are from the durvalumab vs. placebo groups.
Primary Outcomes
- Median progression-free survival
- 16.8 vs. 5.6 months (HR 0.52; two-sided P<0.001)
Secondary Outcomes
- Time to death or distant metastasis
- 23.2 vs. 14.6 months (HR 0.52; P<0.001)
- Patients alive without disease progression at 12 months
- 55.9% vs. 35.3%
- Objective response rate
- 28.4% vs. 16.0% (P<0.001).
Subgroup Analysis
Subgroup analysis of PD-L1 expression status before chemoradiotherapy was conducted. For patients with a PD-L1 expression level of <25%, the PFS benefit was maintained (HR 0.59). For a PD-L1 expression level of >25% a PFS benefit was also observed (HR 0.41).
Adverse Events
- Adverse events of any cause and grade
- 96.8% vs. 94.9%
- Grade 3 or 4 adverse events
- 29.9% vs. 26.1%
- Discontinuation due to adverse events occurred
- 15.4% vs. 9.8%
- Serious adverse events
- 28.6% vs. 22.6%
- Death due to adverse events
- 4.4% vs. 5.6%
Criticisms
- Industry conflicts,
Funding
- Funding provided by the sponsor, AstraZeneca.
- Medical writing support was funded by the sponsor.