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PACIFIC Trial: 5-Year Survival Outcomes With Durvalumab After Chemoradiotherapy in Stage III NSCLC


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As reported in the Journal of Clinical Oncology by Spigel et al, long-term follow-up of the phase III PACIFIC trial has shown maintained progression-free and overall survival benefits with consolidation durvalumab vs placebo after chemoradiotherapy in unresectable stage III non–small cell lung cancer (NSCLC), with estimated 5-year rates of 43% for overall survival and 33% for progression-free survival in the durvalumab group.

Interim analysis of progression-free survival in the PACIFIC trial supported the February 2018 approval of durvalumab for the treatment of unresectable stage III NSCLC that has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

Study Details

In the double-blind trial, 713 patients (irrespective of PD-L1 expression status) with no disease progression after concurrent platinum-based chemotherapy and radiotherapy were randomly assigned 2:1 to receive durvalumab at 10 mg/kg every 2 weeks (n = 476; 473 received treatment) or placebo (n = 237; 236 received treatment) for 12 months. Randomization was stratified by age, sex, and smoking history.

In primary analyses, durvalumab was associated with significant improvements in overall survival (stratified hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.53–0.87, P = .00251) and progression-free survival on blinded independent central review (stratified HR = 0.52, 95% CI = 0.42–0.65, P < .0001).

Updated Survival Outcomes

As of data cutoff (January 2021), median follow-up was 34.2 months (range = 0.2–74.7 months) among all randomly assigned patients and 61.6 months (range = 0.4–74.7 months) among censored patients (patients last known to be alive).

Median overall survival was 47.5 months (95% CI = 38.1–52.9 months) in the durvalumab group vs 29.1 months (95% CI = 22.1–35.1 months) in the placebo group (stratified HR = 0.72, 95% CI = 0.59–0.89). Estimated 5-year overall survival was 42.9% (95% CI = 38.2%–47.4%) vs 33.4% (95% CI = 27.3%–39.6%). 

For stratification subgroups, hazard ratios were 0.66 (95% CI = 0.50–0.87) for age < 65 years and 0.79 (95% CI = 0.60–1.05) for age ≥ 65 years; 0.75 (95% CI = 0.59–0.95) for males and 0.64 (95% CI = 0.44–0.94) for females; and 0.75 (95% CI = 0.61–0.93) for ever-smokers and 0.42 (95% CI = 0.21–0.82) for never-smokers. In post hoc analysis, hazard ratios were 0.61 (95% CI = 0.44–0.85) for PD-L1 expression ≥ 1% and 1.15 (95% CI = 0.75–1.75) for PD-L1 expression < 1%.

Median progression-free survival was 16.9 months (95% CI = 13.0–23.9 months) in the durvalumab group vs 5.6 months (95% CI = 4.8–7.7 months) in the placebo group (stratified HR = 0.55, 95% CI = 0.45–0.68. Estimated 5-year progression-free survival was 33.1% (95% CI = 28.0%–38.2%) vs 19.0% (95% CI = 13.6%–25.2%).

For stratification subgroups, hazard ratios were 0.46 (95% CI = 0.36–0.60) for age < 65 years and 0.76 (95% CI = 0.57–1.01) for age ≥ 65 years; 0.61 (95% CI = 0.48–0.76) for males and 0.52 (95% CI = 0.36–0.74) for females; and 0.61 (95% CI = 0.50–0.75) for ever-smokers and 0.33 (95% CI = 0.17–0.63) for never-smokers. In post hoc analysis, hazard ratios were 0.47 (95% CI = 0.35–0.64) for PD-L1 expression ≥ 1% and 0.80 (95% CI = 0.53–1.20) for PD-L1 expression < 1%.

Overall, 48.5% of the durvalumab group vs 58.6% of the placebo group received at least one subsequent anticancer therapy after discontinuing study treatment, most commonly chemotherapy (33.0% vs 35.9%). Subsequent immunotherapy was received by 12.6% vs 29.1% of patients. 

KEY POINTS

  • Estimated 5-year overall survival was 42.9% in the durvalumab group vs 33.4% in the placebo group.
  • Estimated 5-year progression-free survival was 33.1% vs 19.0%.

The investigators concluded: “These updated analyses demonstrate robust and sustained [overall survival] and durable [progression-free survival] benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years, and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.”

David R. Spigel, MD, of Sarah Cannon Research Institute/Tennessee Oncology, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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