International journal of radiation oncology, biology, physics · 2023
Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis.
Рандомизированное исследованиеКлиническое исследование II фазыСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Rimner Andreas, Moore Zachary R, Lobaugh Stephanie, Geyer Alexander, Gelblum Daphna Y, Abdulnour Raja-Elie E, Shepherd Annemarie F, Shaverdian Narek, Wu Abraham J, Cuaron John, Chaft Jamie E, Zauderer Marjorie G, Eng Juliana, Riely Gregory J, Rudin Charles M, Els Nicholas Vander, Chawla Mohit, McCune Megan, Li Henry, Jones David R, Sopka Dennis M, Simone Charles B, Mak Raymond, Weinhouse Gerald L, Liao Zhongxing, Gomez Daniel R, Zhang Zhigang, Paik Paul K
Аннотация
PURPOSE: Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP.
METHODS AND MATERIALS: In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual.
RESULTS: Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism.
CONCLUSIONS: There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP.
METHODS AND MATERIALS: In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual.
RESULTS: Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism.
CONCLUSIONS: There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP.