LBA1 Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III NSCLC: Final results from PACIFIC-2

The PACIFIC trial established consolidation durvalumab (D) after chemoradiotherapy (CRT) as SoC for pts with unresectable stage III NSCLC. However, up to 30% of pts are ineligible due to progression during/shortly after CRT or inadequate recovery from CRT-related toxicity. The phase III PACIFIC-2 trial evaluated D initiated concurrently with platinum-based concurrent CRT (cCRT) followed by consolidation D, compared with cCRT alone, in pts with unresectable stage III NSCLC. PACIFIC-2 (NCT03519971) was a randomized double-blind study. Treatment (Tx)-naïve pts with WHO PS 0/1 and histologically/cytologically confirmed stage III NSCLC were randomized (2:1) to receive SoC cCRT concurrently with D or placebo (PBO) IV Q4W, stratified by age and disease stage. Pts then received consolidation D/PBO until progression, unacceptable toxicity, consent withdrawal, or other discontinuation criteria. The primary endpoint was PFS (BICR; RECIST v1.1). 327/328 randomized pts received Tx (D arm, n=219; PBO arm, n=108). A higher % of pts in the D vs PBO arm had T4 tumors (57.5% vs 48.6%) and squamous histology (55.3% vs 47.7%). As of 7 Sep 2023 (data cutoff), median follow-up in all (censored) pts was 30.5 (55.5) months. There was a trend (not statistically significant) toward improved PFS with D vs PBO (HR, 0.85; 95% CI: 0.65–1.12; P=0.247); median PFS was 13.8 vs 9.4 months. There was no significant difference in OS (HR, 1.03; 95% CI: 0.78–1.39; P=0.823); median OS was 36.4 vs 29.5 months. Max grade 3/4 any-cause AEs occurred in 53.4% vs 59.3% with D vs PBO; 25.6% vs 12.0% had AEs that led to discontinuation of D/PBO (14.2% vs 5.6% in the first 4 months); 47.0% vs 51.9% had serious AEs; and 13.7% vs 10.2% had AEs with outcome of death. Pneumonitis/radiation pneumonitis occurred in 28.8% vs 28.7%. In PACIFIC-2, concurrent D and CRT did not improve outcomes vs CRT alone. Overall, safety and tolerability were consistent with the known profiles for D and CRT, although one quarter of pts had AEs leading to discontinuation of D, the majority of which occurred in the first 4 months. Consolidation D remains SoC for pts with unresectable stage III NSCLC who do not progress on definitive CRT.