LBA61 Durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (pts) with unresectable stage III NSCLC: Final analysis from PACIFIC-6

In the phase 3, placebo-controlled PACIFIC trial, durva after concurrent CRT (cCRT) significantly improved survival in pts with unresectable Stage III NSCLC, with manageable safety. As many pts are considered unsuitable for cCRT, the phase 2 PACIFIC-6 trial (NCT03693300) assessed safety and efficacy with durva after sequential CRT (sCRT); interim data indicated this approach had a similar safety profile to that with durva after cCRT in PACIFIC with encouraging preliminary efficacy. We report the final analysis from PACIFIC-6. Pts with unresectable Stage III NSCLC, ECOG performance status (PS) ≤2, and no progression after platinum-based sCRT were enrolled to receive durva 1500 mg IV, every 4 wk for up to 24 mo, or until progression, unacceptable toxicity, or consent withdrawal. The primary endpoint (reported previously) was the incidence of grade 3/4 possibly related AEs (PRAEs) occurring within 6 mo. Secondary endpoints included OS and PFS (investigator-assessed; RECIST v1.1), analysed by Kaplan–Meier method. As of Mar 20, 2023, 117 pts were enrolled. Most had PS 1/2 (59.8%; PS 1, n=67; PS 2, n=3), were aged ≥65 yr (65.8%; age range: 39–85 yr), and had stage IIIB/IIIC NSCLC (63.2%). Nearly all had past/present comorbidities (98.3%), mostly vascular (59.0%), respiratory (53.0%) and metabolic (51.3%) disorders. Median treatment duration was 41.0 wk (range: 4–108). Overall, 4.3% (95% CI: 1.4–9.7) of pts had grade 3/4 PRAEs within 6 mo, and 6.0% had grade 3/4 PRAEs during the entire study period (1 pt had a PRAE with outcome of death). Pneumonitis was the most frequently reported PRAE of any grade (17.1%) and grade 3/4 (1.7%). 27.4% of pts discontinued durva due to AEs of any cause. Median duration of follow-up among pts censored for OS was 32.6 mo (range: 4.4–45.7). Median OS was 39.0 mo (95% CI: 30.6–not calculable), the 3-yr OS rate was 56.5% (95% CI: 46.4–65.5), and median PFS was 13.1 mo (95% CI: 7.4–19.9). Durva after sCRT maintained a similar safety profile to that seen with durva after cCRT in PACIFIC and demonstrated encouraging efficacy in a frailer population, supporting use of this approach for pts who are considered unsuitable for cCRT.