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. 

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.