Patient Evaluation of Durvalumab Treatment Results

Durvalumab and the PACIFIC Study

Durvalumab is a selective human monoclonal IgG1 antibody against the programmed cell death ligand-1 (PD-L1) receptor, enabling T lymphocytes to recognize and destroy tumor cells. In the Czech Republic, it is approved as monotherapy for the treatment of adult patients with locally advanced unresectable NSCLC expressing PD-L1 on ≥ 1% of tumor cells if the disease has not progressed after platinum-based chemoradiotherapy.

PACIFIC is a randomized, double-blind, placebo-controlled phase III clinical trial investigating the efficacy of durvalumab as consolidation therapy in patients with unresectable locally advanced stage III NSCLC who did not experience disease progression after concurrent platinum-based chemoradiotherapy. The primary objectives of the study were PFS and overall survival (OS). Previously published analyses demonstrated significantly longer PFS and OS; this article provides analysis of one of the predefined secondary objectives − patient-reported outcomes (PRO). Standardized assessment of patient-reported outcomes is crucial for evaluating the impact of the disease and therapy on patients' quality of life and for rational treatment management.

PRO Assessment Methodology in the PACIFIC Study

Patient-reported symptoms, performance, and overall health status were assessed using the general quality of life questionnaire QLQ-C30 (Quality of Life Questionnaire-Core 30) version 3, developed by the Quality of Life Group within the European Organisation for Research and Treatment of Cancer (EORTC), and its lung cancer module QLQ-LC13 (Quality of Life Questionnaire − Lung Cancer 13).

Questionnaires were filled out by the patients at the time of randomization, in weeks 4 and 8, then every 8 weeks for the first 48 weeks of therapy, and subsequently every 12 weeks until disease progression. Changes in key symptoms were assessed using a mixed model for repeated measures (MMRM) and time-to-event analyses. A change of 10 points from the baseline assessment was considered clinically significant.

Results

More than 79% of patients in the durvalumab-treated group and more than 82% of patients in the placebo group completed all questionnaires during the first 48 weeks from randomization. Within 12 months from randomization, there were no clinically significant changes in observed key symptoms (cough, dyspnea, chest pain, fatigue, loss of appetite, physical performance, and overall health status) in any group. The difference between the two groups in adjusted mean changes for cough was 1.1 (95% confidence interval [CI] –1.89 to 4.11), dyspnea 1.6 (95% CI –0.58 to 3.87), chest pain 0.4 (95% CI –2.13 to 2.93), fatigue 2.2 (95% CI –0.38 to 4.78), loss of appetite 1.2 (95% CI –1.27 to 3.67), physical performance –1.9 (95% CI –3.91 to 0.15), and overall health status 0.8 (95% CI –1.55 to 3.14). None of these differences between the two groups were clinically significant.

Conclusion

The results of this secondary analysis suggest that the clinical effect of durvalumab treatment can be achieved without deterioration in patient-reported outcomes, and thus without a decrease in patient-reported quality of life.

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Sources:
1. Hui R., Özgüroğlu M., Villegas A. et al. Patient-reported outcomes with durvalumab after chemoradiotherapy in stage III, unresectable non-small-cell lung cancer (PACIFIC): a randomised, controlled, phase 3 study. Lancet Oncol 2019 Dec; 20 (12): 1670−1680, doi: 10.1016/S1470-2045(19)30519-4.
2. SPC Imfinzi. Last revision date: 21. 2. 2020. Available at: www.ema.europa.eu/en/documents/product-information/imfizi-epar-product-information_cs.pdf