CLO22-052: A Tale of Two Schedules: A Study of the Efficacy and Toxicity Outcomes of Extended Durvalumab Dosing in Patients with Stage III Unresectable Non-Small Cell Lung Cancer (NSCLC)

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Lilian Hanna Queen's University, Kingston, Canada

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Gordon Taylor Moffat Queen's University, Kingston, Canada

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Wilma Hopman Queen's University, Kingston, Canada

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Pierre-Olivier Gaudreau Queen's University, Kingston, Canada

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Andrea S. Fung Queen's University, Kingston, Canada

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Background: The addition of durvalumab following chemoradiation in unresectable Stage III NSCLC has led to improved cancer outcomes. The schedule of administration has largely been determined by pharmacokinetic studies with a paucity of data exploring alternate dosing schedules. The COVID-19 pandemic created a need to cut down on patient visits, thus allowing incorporation of extended dosing (ED) of durvalumab (20mg/kg IV every 4 weeks) into clinical practice. The current study evaluates real-world efficacy and safety of ED vs. standard dosing (SD) of durvalumab. Methods: All NSCLC patients treated at the Cancer Centre of Southeastern Ontario with maintenance durvalumab (ED: 20mg/kg IV every 4 weeks, or SD: 10mg/kg IV every 2 weeks) from January 2018 to December 2020 were included. Patient characteristics, treatment and toxicity outcomes were evaluated through chart review. Treatment outcomes and adverse events were compared between ED and SD groups. Analysis included multivariable Cox proportional hazards modelling. Results: A total of 35 patients were included, with 15 (42%) who switched to the ED schedule. There were a higher proportion of younger (<65 yr) patients in the ED group (60% vs 25%, p=0.036). Recurrence rates were higher in the ED group 27% vs. 10% in the SD group. The pattern of recurrence in the ED group had a predilection for brain metastasis, with 33% compared to 5% in the SD group (p=0.064). Despite this, 93% of patients were alive in the ED group vs. 80% in the SD group at data cutoff (p=0.3). Treatment discontinuation occurred in 47% in the ED group vs. 50% in the SD group, owing to toxicity in 43% of patients in the ED group vs. 80% in the SD group (p=0.16). Grade 3 or higher toxicities accounted for 27% of toxicities in the SD group vs. none reported in the ED group. All patients in the ED group were re-challenged with durvalumab at a later date vs. only 33% of patients in the SD group (p=0.08). Conclusion: There was a higher rate of toxicity necessitating discontinuation of durvalumab in the SD group. This might have impacted the clinical decision-making to switch to ED, thereby contributing to a possible selection bias. A higher proportion of patients discontinued durvalumab due to progression in the ED group, and there was a trend towards development of brain metastasis in patients in the ED group. Results are limited by a small sample size and should be further validated in larger cohorts.

Corresponding Author: Lilian Hanna, DO
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