PACIFIC
Durvalumab versus placebo as consolidation after concurrent platinum-based chemoradiotherapy in unresectable stage III non-small-cell lung cancer
Phase 3N = 713NCT02125461
- Population
- Stage III, unresectable non-small-cell lung cancer without disease progression after two or more cycles of platinum-based concurrent chemoradiotherapy; WHO performance status 0 or 1; any PD-L1 status
- Design
- Randomised 2:1, placebo-controlled phase 3 trial. Durvalumab 10 mg per kilogram of body weight or matching placebo intravenously every 2 weeks for up to 12 months, started 1 to 42 days after chemoradiotherapy; randomisation stratified by age, sex and smoking history. 709 of 713 randomised patients received study treatment (473 durvalumab, 236 placebo).
- Primary endpoint
- PFS, OS
- Arms
- Durvalumab (experimental, n = 476): Durvalumab 10 mg per kilogram intravenously every 2 weeks for up to 12 months
- Placebo (control, n = 237): Matching placebo intravenously every 2 weeks for up to 12 months
- People
- Antonia SJ, PACIFIC Investigators
PFSHR 0.52 (95% CI 0.42–0.65)Δ median PFS+11.2 monthsΔ 12-month PFS+20.6 pointsΔ ORR+12.4 pointsOSHR 0.68Δ 24-month OS+10.7 points
Show the numbers
| Endpoint | Analysis | Durvalumab | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N = 713)Progression-free survival assessed by blinded independent central review | primaryAntonia 2017 | median 16.8 months (13.0–18.1); 55.9% at 12 mo; 44.2% at 18 mo | median 5.6 months (4.6–7.8); 35.3% at 12 mo; 27% at 18 mo | HR 0.52 (95% CI 0.42–0.65)P<0.001Co-primary endpoint. The abstract gives the 12-month PFS rates (55.9% vs 35.3%) and 18-month rates (44.2% vs 27.0%) without confidence intervals. |
| ORRRandomised patients (N = 713) | primaryAntonia 2017 | 28.4% | 16% | P<0.001Secondary endpoint. The abstract also gives the proportion with an ongoing response at 18 months (72.8% vs 46.8%). |
| OSRandomised patients (N = 713) | primarymedian follow-up 25.2 monthsAntonia 2018 | 66.3% at 2 y (61.7–70.4%) | 55.6% at 2 y (48.9–61.8%) | HR 0.68P=0.0025Second primary endpoint. The abstract gives the hazard ratio for death as 0.68 with a 99.73% CI of 0.47 to 0.997 (P=0.0025), so no ci95 is entered; the difference in 24-month OS rates has a two-sided P=0.005. |
| PFSRandomised patients (N = 713) | long term-updatemedian follow-up 25.2 monthsAntonia 2018 | median 17.2 months | median 5.6 months | HR 0.51 (95% CI 0.41–0.63)Reported in the overall-survival paper as similar to the earlier PFS analysis. |
| OS | exploratorymedian follow-up 34.2 monthsSpigel 2022 | median 47.5 months; 42.9% at 5 y (38.2–47.4%) | median 29.1 months; 33.4% at 5 y (27.3–39.6%) | HR 0.72 (95% CI 0.59–0.89)The authors describe these as updated, exploratory analyses. Median follow-up was 34.2 months for all patients and 61.6 months for censored patients. |
| PFSProgression-free survival by blinded independent central review (RECIST v1.1) | exploratorymedian follow-up 34.2 monthsSpigel 2022 | median 16.9 months; 33.1% at 5 y (28.0–38.2%) | median 5.6 months; 19% at 5 y (13.6–25.2%) | HR 0.55 (95% CI 0.45–0.68)Updated, exploratory analysis; median follow-up 34.2 months for all patients. |
| Endpoint | Analysis | Durvalumab | Placebo | Effect |
|---|---|---|---|---|
| PFSRandomised patients (N = 713)Progression-free survival assessed by blinded independent central review | primaryAntonia 2017 | median 16.8 months (13.0–18.1); 55.9% at 12 mo; 44.2% at 18 mo | median 5.6 months (4.6–7.8); 35.3% at 12 mo; 27% at 18 mo | HR 0.52 (95% CI 0.42–0.65)P<0.001Co-primary endpoint. The abstract gives the 12-month PFS rates (55.9% vs 35.3%) and 18-month rates (44.2% vs 27.0%) without confidence intervals. |
| ORRRandomised patients (N = 713) | primaryAntonia 2017 | 28.4% | 16% | P<0.001Secondary endpoint. The abstract also gives the proportion with an ongoing response at 18 months (72.8% vs 46.8%). |
| OSRandomised patients (N = 713) | primarymedian follow-up 25.2 monthsAntonia 2018 | 66.3% at 2 y (61.7–70.4%) | 55.6% at 2 y (48.9–61.8%) | HR 0.68P=0.0025Second primary endpoint. The abstract gives the hazard ratio for death as 0.68 with a 99.73% CI of 0.47 to 0.997 (P=0.0025), so no ci95 is entered; the difference in 24-month OS rates has a two-sided P=0.005. |
| PFSRandomised patients (N = 713) | long term-updatemedian follow-up 25.2 monthsAntonia 2018 | median 17.2 months | median 5.6 months | HR 0.51 (95% CI 0.41–0.63)Reported in the overall-survival paper as similar to the earlier PFS analysis. |
| OS | exploratorymedian follow-up 34.2 monthsSpigel 2022 | median 47.5 months; 42.9% at 5 y (38.2–47.4%) | median 29.1 months; 33.4% at 5 y (27.3–39.6%) | HR 0.72 (95% CI 0.59–0.89)The authors describe these as updated, exploratory analyses. Median follow-up was 34.2 months for all patients and 61.6 months for censored patients. |
| PFSProgression-free survival by blinded independent central review (RECIST v1.1) | exploratorymedian follow-up 34.2 monthsSpigel 2022 | median 16.9 months; 33.1% at 5 y (28.0–38.2%) | median 5.6 months; 19% at 5 y (13.6–25.2%) | HR 0.55 (95% CI 0.45–0.68)Updated, exploratory analysis; median follow-up 34.2 months for all patients. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.52 | 0.42–0.65 |
| PFS | 0.51 | 0.41–0.63 |
| OS | 0.72 | 0.59–0.89 |
| PFS | 0.55 | 0.45–0.68 |
- Durvalumab (experimental)
- Placebo (control)
Data table (modelled values)
| Months | Durvalumab | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 80.6% | 70.6% |
| 10 | 62.1% | 43.3% |
| 15 | 49.4% | 29.6% |
| 19 | 44.2% | 27.0% |
- Durvalumab (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 64.2% | 25.6% |
| 22 | 41.2% | 6.6% |
| 32 | 27.5% | 1.9% |
| 43 | 17.7% | 0.5% |
Appears in
Sources
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919-1929.
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.
Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022;40(12):1301-1311.