Nintedanib and prednisone taper combo improves pulmonary exacerbations in radiation pneumonitis
USA: Adding nintedanib to a prednisone taper improves pulmonary exacerbations in grade 2 or higher (G2+) radiation pneumonitis (RP) patients, according to findings from a randomized, phase II, placebo-controlled trial. The trial's results were published in the International Journal of Radiation Oncology - Biology - Physics (IJROBP).
In patients who received nintedanib + prednisone taper, freedom from exacerbation at one year was 72%, and 40% in those who received placebo + prednisone taper. "Patients who received nintedanib were more likely to be free from acute pulmonary exacerbations within one year of study enrollment," the researchers wrote.
Radiation pneumonitis is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib treats idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the RP's subacute phase. Andreas Rimner, Weill Cornell Medical Center New York, NY, USA, and colleagues aimed to determine the safety and efficacy of nintedanib addition to a prednisone taper compared to a prednisone taper alone in pulmonary exacerbations reduction in patients with G2+ radiation pneumonitis.
The randomized, phase II, double-blinded, placebo-controlled trial included patients with newly diagnosed G2+ radiation pneumonitis. They were randomized in the 1:1 to nintedanib or placebo ratio in addition to a standard 8-week prednisone taper.
Freedom from pulmonary exacerbations at one year was determined (primary endpoint). Secondary endpoints included pulmonary function tests and patient-reported outcomes. The probability of freedom from pulmonary exacerbations was estimated by Kaplan-Meier analysis. However, owing to slow accrual, the study was terminated early.
The study led to the following findings:
· Enrollment of 34 patients as done between October 2015 and February 2020. Of 30 patients were randomized, out of which 18 were allocated to the experimental Arm A (nintedanib + prednisone taper) and 12 to control Arm B (prednisone taper + placebo).
· In Arm A, freedom from exacerbation at one year was 72% and 40% in Arm B.
· In Arm A, 16 G2+ adverse events were probably related to treatment versus five in the placebo arm.
· In arm A, there were three deaths during the study period due to cardiac failure, progressive respiratory failure, and pulmonary embolism, respectively.
"We observed an improvement in pulmonary exacerbations by adding nintedanib to a prednisone taper," the authors concluded. "Further investigation is warranted for nintedanib use for the treatment of RP."
Reference:
Rimner A, Moore ZR, Lobaugh S, Geyer A, Gelblum DY, Abdulnour RE, Shepherd AF, Shaverdian N, Wu AJ, Cuaron J, Chaft JE, Zauderer MG, Eng J, Riely GJ, Rudin CM, Els NV, Chawla M, McCune M, Li H, Jones DR, Sopka DM, Simone CB 2nd, Mak R, Weinhouse GL, Liao Z, Gomez DR, Zhang Z, Paik PK. Randomized, phase II, placebo-controlled trial of nintedanib for the treatment of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2023 Mar 6:S0360-3016(23)00177-3. doi: 10.1016/j.ijrobp.2023.02.030. Epub ahead of print. PMID: 36889516.
