Abstract CT213: Impact of smoking on outcomes with durvalumab following chemoradiotherapy in unresectable Stage III NSCLC (PACIFIC)
Authors: Planchard David , Özgüroğlu Mustafa , Daniel Davey , Villegas Augusto , Vicente David , Murakami Shuji , Hui Rina , Faivre-Finn Corinne , Paz-Ares Luis , Wu Yi-Long , Macpherson Euan , Newton Michael , Dennis Phillip , Antonia Scott J. 
Published: September 2020

Abstract
Background: The phase 3 PACIFIC trial established durvalumab (durva) after concurrent chemoradiotherapy (cCRT) as standard of care for unresectable Stage III NSCLC. We report exploratory, post-hoc analyses to assess the impact of smoking status on outcomes in pts from PACIFIC.
Methods: PACIFIC was a double-blind trial of pts without disease progression after platinum-based cCRT (≥2 cycles). Pts were randomized 2:1 to receive durva 10 mg/kg or placebo (pbo) intravenously q2w for ≤12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS and OS. Treatment effects (HRs) within subgroups of smokers (current and former) and never smokers were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians).
Results: Of 713 randomized pts, 64 (9%) were never smokers (Table). Baseline characteristics were broadly well balanced; however, irrespective of study arm, proportionally more never smokers (vs smokers) were female, Asian, and had non-squamous histology. Among never smokers, proportionally more pts in the pbo arm vs durva arm were Stage IIIB (52% vs 40%) and had received induction chemotherapy (33% vs 21%). PFS and OS were improved with durva vs pbo in both smokers and never smokers (Table). The incidence of grade 3/4 AEs was proportionally higher in smokers (vs never smokers) in both the durva (34% vs 23%) and pbo arms (30% vs 14%). In contrast, the incidence of any-grade pneumonitis/radiation pneumonitis was proportionally higher in never smokers (vs smokers) in the durva (56% vs 32% [grade 3/4: 7% vs 3%]) and pbo arms (48% vs 23% [grade 3/4: 5% vs 2%]).
SmokersNever SmokersDurvalumab (n=433)Placebo (n=216)Durvalumab(n=43)Placebo(n=21)# of PFS events (%)197 (45.5)140 (64.8)17 (39.5)17 (81.0)PFS HR (95% CI)0.59 (0.47-0.73)0.29 (0.15-0.57)Median PFS (95% CI), mo16.8 (12.3-17.8)6.4 (4.9-8.7)NR (7.2-NE)3.0 (1.8-5.6)12-mo PFS (95% CI), %55.7 (50.6-60.5)37.5 (30.8-44.2)57.8 (40.8-71.5)8.4 (0.6-29.9)18-mo PFS (95% CI), %43.1 (36.2-49.7)28.4 (20.9-36.4)57.8 (40.8-71.5)NR (NE-NE)*# of OS events (%)169 (39.0)103 (47.7)14 (32.6)13 (61.9)OS HR (95% CI)0.72 (0.56-0.92)0.35 (0.16-0.76)Median OS (95% CI), moNR (33.2-NR)29.1 (23.5-NR)34.9 (28.3-NR)18.7 (12.5-31.0)12-mo OS (95% CI), %82.8 (78.9-86.1)75.3 (68.9-80.6)86.0 (71.6-93.5)75.4 (50.6-89.0)24-mo OS (95% CI), %65.5 (60.7-69.8)56.7 (49.7-63.2)74.1 (58.0-84.7)43.1 (21.1-63.4)*Kaplan-Meier undefined; no patients at risk at 18 mo.PFS was assessed by blinded independent central review (RECIST v1.1).Median follow up for PFS = 14.5 mo (DCO for the primary analysis of PFS: 13 Feb 2017).Median follow up for OS = 25.2 mo (DCO for the primary analysis of OS: 22 Mar 2018).CI, confidence interval; DCO, data cutoff; HR, hazard ratio; mo, months; NR, not reached; NE, not estimable; OS, overall survival; PFS, progression-free survival.
Conclusions: Consistent with the ITT population, durva improved PFS and OS in both smokers and never smokers with unresectable Stage III NSCLC who had received prior cCRT. The small size of the never smokers subgroup and imbalances in baseline characteristics preclude robust conclusions regarding inter-subgroup differences in clinical outcomes.
Citation Format: David Planchard, Mustafa Özgüroğlu, Davey Daniel, Augusto Villegas, David Vicente, Shuji Murakami, Rina Hui, Corinne Faivre-Finn, Luis Paz-Ares, Yi-Long Wu, Euan Macpherson, Michael Newton, Phillip Dennis, Scott J. Antonia. Impact of smoking on outcomes with durvalumab following chemoradiotherapy in unresectable Stage III NSCLC (PACIFIC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT213.