Randomized phase 2 placebo-controlled trial of nintedanib for the treatment of radiation pneumonitis Journal Article
| Authors: | Rimner, A.; Moore, Z. R.; Lobaugh, S.; Geyer, A.; Gelblum, D. Y.; Abdulnour, R. E. E.; Shepherd, A. F.; Shaverdian, N.; Wu, A. J.; Cuaron, J.; Chaft, J. E.; Zauderer, M. G.; Eng, J.; Riely, G. J.; Rudin, C. M.; Els, N. V.; Chawla, M.; McCune, M.; Li, H.; Jones, D. R.; Sopka, D. M.; Simone, C. B. 2nd; Mak, R.; Weinhouse, G. L.; Liao, Z.; Gomez, D. R.; Zhang, Z.; Paik, P. K. |
| Article Title: | Randomized phase 2 placebo-controlled trial of nintedanib for the treatment of radiation pneumonitis |
| Abstract: | 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. © 2023 Elsevier Inc. |
| Keywords: | adult; clinical article; controlled study; aged; prednisone; clinical trial; fatigue; placebo; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; monotherapy; side effect; cancer radiotherapy; prospective study; anorexia; phase 2 clinical trial; protein kinase inhibitor; nausea; randomized controlled trial; thrombocytopenia; radiotherapy; coughing; dyspnea; rash; protein kinase inhibitors; hypoxia; lung embolism; confidence interval; disease progression; heart failure; multicenter study; thromboembolism; vein thrombosis; mesothelioma; pleura effusion; patient-reported outcomes; thymoma; lung infection; double blind procedure; double-blind method; pericardial effusion; idiopathic pulmonary fibrosis; lung function test; disease exacerbation; lymphocyte count; radiation pneumonia; platelet count; respiratory failure; small cell lung cancer; non small cell lung cancer; phase 2; dose limiting toxicity; radiation pneumonitis; patient-reported outcome; corticosteroid therapy; controlled trial; afatinib; combination drug therapy; methods and materials; humans; human; male; female; article; nintedanib; pembrolizumab; durvalumab; pathophysiological; malignant neoplasm; pulmonary function test |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 116 |
| Issue: | 5 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-08-01 |
| Start Page: | 1091 |
| End Page: | 1099 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2023.02.030 |
| PUBMED: | 36889516 |
| PROVIDER: | scopus |
| PMCID: | PMC10751877 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Andreas Rimner -- Source: Scopus |
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