PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer
Giving the immunotherapy durvalumab for a year after chemoradiotherapy for unresectable stage III lung cancer tripled the time to progression and raised five-year survival from about a third to over 40%.
Double-blind, placebo-controlled phase 3 trial of 713 patients with unresectable stage III NSCLC who had not progressed after concurrent platinum-based chemoradiotherapy, randomised 2:1 to up to 12 months of durvalumab or placebo. Co-primary endpoints were PFS and overall survival.
Median PFS was 16.8 vs 5.6 months (HR 0.52) and overall survival was significantly improved (HR 0.68 in the 2018 report). Five-year OS was 42.9% vs 33.4%. It was the first change in stage III standard of care in two decades and the model for consolidation immunotherapy in small-cell lung cancer (ADRIATIC) and other tumours.
- Median PFS 16.8 vs 5.6 months; HR 0.52 (95% CI 0.42-0.65).
- Overall survival (2018): HR 0.68; 24-month OS 66.3% vs 55.6%.
- Five-year update (JCO 2022): OS 42.9% vs 33.4%; PFS 33.1% vs 19.0%.
- Grade 3-4 pneumonitis or radiation pneumonitis 3.4% vs 2.6%; any-grade pneumonitis about 34% vs 25%.
- Post hoc analysis suggested little benefit in PD-L1 below 1%, leading the EMA (but not FDA) to restrict the label to PD-L1 of 1% or more.
Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).
- PD-L1 status was not required for enrolment and the subgroup analysis by PD-L1 below 1% was unplanned and post hoc.
- Patients had to have completed chemoradiotherapy without progression, a selected fitter population.
- Combined radiation and immune pneumonitis requires careful monitoring, especially in Asian populations where rates were higher.
- The trial did not test whether concurrent immunotherapy during radiotherapy is better; PACIFIC-2 was negative.