Evaluation of the safety and effectiveness of switching from standard to extended interval dosing for durvalumab in unresectable stage III non-small cell lung cancer.
Authors: Mac Stephanie , Hui Rita L. , Nishimura Kris N. , Tan Evelyn , Chiu Timothy , Shen Diana D. 
Published: June 2021

e20501

Background: In 2018, the FDA approved durvalumab with weight-based dosing of 10 mg/kg every 2 weeks for unresectable, Stage III non-small cell lung cancer (NSCLC) following chemoradiation therapy based on the results of the PACIFIC trial. The feasibility of a fixed, extended interval dosing was assessed in a population pharmacokinetics (PK) modeling study. The PK model compared the approved weight-based dosing vs. flat-dosing at 750 mg every 2 weeks or 1,500 mg every 4 weeks and showed similar median steady-state exposure. At our institution, patients were switched from the standard every 2 weeks to the extended every 4 weeks dosing interval due to the 2019 coronavirus disease pandemic to minimize patient visits. To our knowledge, our study offers the first real-word data on patients who switched to an extended dosing interval of durvalumab. Methods: This was an observational study that included adults with a diagnosis of unresectable, Stage III NSCLC and who received treatment with durvalumab 02-16-2018 through 08-31-2020. The study group (“switcher”) included patients who switched from every 2 weeks to every 4 weeks dosing while the control group (“non-switcher”) remained on every 2 weeks interval. Patients were followed until therapy discontinuation, death, or end of data collection date (12-31-2020), whichever occurred first. Both groups were matched on age, sex, and durvalumab exposure. The primary outcome was to evaluate any differences in the incidence of immune-mediated adverse events (IMAE) for patients receiving standard interval dosing of durvalumab compared to patients that switched to extended interval dosing. The secondary outcome was to assess any differences in objective response (OR). Worsening OR was defined as response of scan prior to last durvalumab dose compared to baseline scan. The rate of IMAE and worsening OR were compared using Fisher’s exact test. Conditional logistic regression was used to estimate odd ratio for IMAE between the two groups. Results: This matched cohort included 16 patients in each of the two groups. The overall mean age was 70±6 years old, 39% were male, 71% were former smokers, 78% had an ECOG performance score of 0-1, 92% had non-squamous histological subtype, and 71% achieved a partial response to concurrent chemoradiation therapy prior to durvalumab. The rate of IMAE was 12.5% in switcher group and 31.3% in non-switchers group (OR 2.5; 95% CI: 0.5, 12.9); p = 0.39). The rate of worsening OR was 60.0% in the switcher group and 41.7% in the non-switcher group (p = 0.67). Conclusions: Though the data are limited, these results may serve as early clinical data validation for the use of extended dosing of durvalumab. Rates of IMAE were not significantly different, but trended higher in the non-switcher group. Similarly, the rate of worsening OR was not significantly different between switchers and non-switchers.