Safety and efficacy outcomes with durvalumab after sequential chemoradiotherapy (sCRT) in stage III, unresectable NSCLC (PACIFIC-6)

In the ph 3, placebo-controlled PACIFIC trial, durvalumab (durva) after concurrent CRT (cCRT) significantly improved survival in pts with Stage III, unresectable NSCLC, with manageable safety. As many pts are ineligible for cCRT, the ph 2 PACIFIC-6 trial (NCT03693300) aims to assess safety with durva after sCRT. We report the primary safety analysis and secondary efficacy analyses from PACIFIC-6. Pts with ECOG PS ≤2 and no progression after platinum-based sCRT were enrolled to receive durva 1500mg IV q4w ≤24 months or until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was safety/tolerability of durva, defined by the incidence of grade 3/4 possibly related AEs (PRAEs) occurring within 6 months of treatment (Tx) initiation. PFS and ORR (investigator assessed; RECIST v1.1), and OS, were secondary endpoints. PFS and OS were analysed by Kaplan–Meier method. As of July 15, 2021, 117 pts were enrolled; 114 (97.4%) had PS 0/1 and 3 (2.6%) had PS 2. Median age was 68.0 years (65.8% were aged ≥65), 62.4% were male and 37.6%/50.4%/11.1% had Stage IIIA/B/C NSCLC. 98.3% had past/present medical conditions, mostly vascular (59.0%), respiratory (53.8%) and metabolic (51.3%) disorders. Median Tx duration was 32.0 weeks (37.6% were ongoing Tx at data cutoff). In all, 94.9% of pts had any AEs and 76.9% had PRAEs. 18.8% had grade 3/4 AEs and 4.3% had grade 3/4 PRAEs (1.7% had grade 3/4 PRAE pneumonitis); all pts with grade 3/4 PRAEs had these events occur within 6 months (4.3%; 95% CI, 1.4–9.7). 21.4% and 16.2% had AEs and PRAEs leading to Tx discontinuation, respectively; pneumonitis was the most common PRAE leading to discontinuation (10.3%). 2 pts (1.7%) had fatal AEs; 1 was a PRAE (pneumonitis). Efficacy outcomes are listed in the table.Table: 108MOEfficacy outcomesAll patients (N=117)*†PS 0/1 cohort (N=114)‡Median PFS, months (95% CI)10.9 (7.3–15.6)13.1 (7.4–16.7)12-month PFS, % (95% CI)49.6 (39.5–58.9)50.1 (39.9–59.5)Median OS, months (95% CI)25.0 (25.0–NC)25.0 (25.0–NC)12-month OS, % (95% CI)84.1 (75.6–89.9)84.6 (76.0–90.3)Confirmed ORR, % (95% CI)§17.1 (11.1–25.8)17.5 (11.4–26.4)*Median follow-up among pts censored for PFS = 11.0 months (range, <0.1–22.3 months).†Median follow-up among pts censored for OS = 13.3 months (range, 4.4–25.6 months). ‡47/114 (41.2%) had PS 0 and 67/114 (58.8%) had PS 1. §95% CI for ORR was calculated using the Clopper–Pearson method. CI, confidence interval; NC, not calculable. Open table in a new tab *Median follow-up among pts censored for PFS = 11.0 months (range, <0.1–22.3 months). †Median follow-up among pts censored for OS = 13.3 months (range, 4.4–25.6 months). ‡47/114 (41.2%) had PS 0 and 67/114 (58.8%) had PS 1. §95% CI for ORR was calculated using the Clopper–Pearson method. CI, confidence interval; NC, not calculable. Durva after sCRT had a similar safety profile to that observed with durva after cCRT in the PACIFIC trial and showed encouraging preliminary efficacy in a frailer and older population.