Background In the PACIFIC study of durvalumab vs. placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), the co-primary endpoint PFS was significantly longer with durvalumab (stratified HR 0.52, 95% CI, 0.42– 0.65; P < 0.0001). PFS benefit with durvalumab was observed regardless of a 65-year age cutoff. Median age at NSCLC diagnosis is 70. We performed subgroup analyses to explore outcomes using a 70-year age cutoff.
Method PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind, all-comers study of patients with WHO PS 0/1 who did not progress following ≥ 2 cycles of platinum-based cCRT. Patients were randomized (2 : 1) 1 – 42 days after cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS and OS. Secondary endpoints included ORR, time to death/distant metastasis (TTDM), and safety. Between treatment endpoint comparisons were performed for patients < 70 and ≥ 70 years.
Result 713 patients were randomized; 78% and 22% were < 70 and ≥ 70 years. Baseline patient and tumor characteristics were well balanced across subgroups. Durvalumab demonstrated PFS benefit compared with placebo, regardless if patients were < 70 years (median 16.9 vs. 5.6 months, HR=0.53, 95% CI: 0.42 – 0.67) or ≥ 70 years (median 12.3 vs. 6.1 months, HR=0.62, 95% CI: 0.41 – 0.95). Durvalumab improved TTDM (< 70 years: HR=0.53, 95% CI: 0.39 – 0.71; ≥ 70 years: HR=0.66, 95% CI: 0.39 – 1.13) and ORR (< 70 years: 27.6% vs. 15.4%; ≥ 70 years: 31.9% vs. 17.6%) regardless of age. Younger patients on durvalumab received treatment longer (median total duration 45.5 vs. 36.0 weeks). Older patients discontinued more due to AEs (durvalumab: 22.0% vs. 13.7%; placebo: 16.1% vs. 7.8%) and had more grade 5 AEs (durvalumab: 10.9% vs. 2.7%; placebo: 9.1% vs. 4.5%). Older patients experienced more all-cause SAEs (42.6% vs. 24.9%) and grade 3/4 AEs (41.6% vs. 29.4%) but fewer AESIs (56.4% vs. 67.9%) than younger patients on durvalumab.
Conclusion: Patients achieved clinical benefit with durvalumab regardless of age. Increased AEs/SAEs observed in older patients across treatments may reflect age/cCRT related morbidity.
Sponsored by AstraZeneca Germany
