Patient-reported Outcomes (pros) with Durvalumab by PD-L1 Expression in Unresectable, Stage III NSCLC (PACIFIC)

Background: In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups. Methods: After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression. Results: Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs. Conclusions: There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study. Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.